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Aproximadamente&#44; 1&#44;5 a 2&#44;0 milh&#245;es e 500&#46;000 novos casos de CL e LV&#44; respectivamente&#44; s&#227;o observados anualmente&#46; A leishmaniose causa cerca de 40 mil mortes por ano<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">3</span></a> e &#233; influenciada por diversos fatores&#44; como origem gen&#233;tica do hospedeiro&#44; aspectos nutricionais&#44; <span class="elsevierStyleItalic">Leishmania</span> spp&#46;&#44; meio ambiente e aspecto imunol&#243;gico&#46;<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">4</span></a> Um estudo recente relatou que as varia&#231;&#245;es gen&#233;ticas do hospedeiro podem desempenhar papel fundamental na suscetibilidade &#224; leishmaniose&#46;<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">5</span></a> Muitos genes foram investigados&#44; evidenciando forte rela&#231;&#227;o entre SNPs e risco de desenvolver leishmaniose&#44; incluindo interferon&#8208;gama &#40;IFN&#8208;G&#41;<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">6</span></a> e interleucina&#8208;6 &#40;IL&#8208;6&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">7</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">A lectina de liga&#231;&#227;o &#224; manose &#40;MBL&#41; &#233; um receptor de reconhecimento de pat&#243;genos &#40;PRR&#41; e desempenha papel cr&#237;tico na imunidade do hospedeiro&#46; A MBL leva &#224; ativa&#231;&#227;o do sistema complemento&#46;<a class="elsevierStyleCrossRefs" href="#bib0240"><span class="elsevierStyleSup">8&#44;9</span></a> Essa prote&#237;na oligom&#233;rica consiste em subunidades estruturais formadas por tr&#234;s polipept&#237;dios id&#234;nticos de 32 kD&#44; cada um contendo uma liga&#231;&#227;o cruzada com a regi&#227;o N&#8208;terminal da ciste&#237;na&#44; col&#225;geno ligado &#224; regi&#227;o do pesco&#231;o e uma regi&#227;o do dom&#237;nio C&#8208;terminal que reconhece carboidratos em microrganismos&#46;<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">10</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Por meio de m&#250;ltiplos dom&#237;nios da lectina&#44; carboidratos como manose &#40;carboidratos de seis carbonos&#41; s&#227;o encontrados na superf&#237;cie de v&#225;rios pat&#243;genos&#44; incluindo <span class="elsevierStyleItalic">Trypanosoma cruzi</span>&#44;<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">11</span></a><span class="elsevierStyleItalic">Plasmodium falciparum</span><a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">12</span></a> e <span class="elsevierStyleItalic">Mycobacterium tuberculosis</span>&#46;<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">13</span></a> Ap&#243;s o reconhecimento dessas mol&#233;culas pela lectina&#44; as serina proteases s&#227;o ativadas para facilitar a opsoniza&#231;&#227;o &#40;fagocitose&#41; pelos macr&#243;fagos e a lise da superf&#237;cie do microrganismo&#46;<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">14</span></a> A forma infecciosa da leishmania &#40;promastigota&#41; &#233; caracterizada pela presen&#231;a de lipofosfoglicanos &#40;GLP&#41; e outras mol&#233;culas como a manose&#46;<a class="elsevierStyleCrossRefs" href="#bib0275"><span class="elsevierStyleSup">15&#44;16</span></a> Esses componentes atuam como padr&#245;es moleculares associados a pat&#243;genos &#40;PAMPs&#41; que s&#227;o reconhecidos pelos componentes do complemento&#46;<a class="elsevierStyleCrossRefs" href="#bib0285"><span class="elsevierStyleSup">17&#44;18</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">O gene <span class="elsevierStyleItalic">MBL2</span> est&#225; localizado no cromossomo 10 &#40;10q11&#46;2&#8208;q21&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">19</span></a> Nesse gene&#44; v&#225;rios SNPs foram identificados&#44; os quais s&#227;o conhecidos por seu efeito funcional que influencia o desenvolvimento de doen&#231;as infecciosas&#46;<a class="elsevierStyleCrossRefs" href="#bib0300"><span class="elsevierStyleSup">20&#8211;22</span></a> Os SNPs funcionais&#44; localizados na regi&#227;o do promotor&#44; como o SNP &#8208;550 H&#47;L &#40;substitui&#231;&#227;o de G<span class="elsevierStyleHsp" style=""></span>&#62; C&#44; rs11003125&#41;&#44; &#8208;221 X&#47;Y &#40;substitui&#231;&#227;o de C<span class="elsevierStyleHsp" style=""></span>&#62; G&#44; rs7096206&#41; e &#43;4 Q&#47;P &#40;A substitui&#231;&#227;o de C<span class="elsevierStyleHsp" style=""></span>&#62; T&#44; rs7095891&#41; localizada na regi&#227;o n&#227;o traduzida&#44; pode regular a taxa de transcri&#231;&#227;o do gene&#46;<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">23</span></a> No primeiro &#233;xon existem tr&#234;s SNPs localizados no c&#243;don 52 CGT<span class="elsevierStyleHsp" style=""></span>&#62; TGT &#40;rs5030737&#41;&#44; c&#243;don 54 GGC<span class="elsevierStyleHsp" style=""></span>&#62; GAC &#40;rs1800450&#41; e c&#243;don 57 GGA<span class="elsevierStyleHsp" style=""></span>&#62; GAA &#40;rs1800451&#41;&#44; correspondendo a altera&#231;&#245;es de amino&#225;cidos entre arginina para ciste&#237;na &#40;Arg52Cys&#44; alelo D&#41;&#44; glicina para &#225;cido asp&#225;rtico &#40;Gly54Asp&#44; alelo B&#41; e glicina para &#225;cido glut&#226;mico &#40;Gly57Glu&#44; alelo C&#41; na regi&#227;o col&#225;gena da cadeia polipept&#237;dica&#44; respectivamente&#46;<a class="elsevierStyleCrossRef" href="#bib0320"><span class="elsevierStyleSup">24</span></a> Esses tr&#234;s polimorfismos formam o sistema AO&#44; no qual o alelo selvagem &#233; descrito como o alelo A&#44; e o alelo O como um mutante&#46; O gen&#243;tipo A&#47;O est&#225; correlacionado com baixos n&#237;veis da prote&#237;na e indetect&#225;vel para o gen&#243;tipo O&#47;O&#46;<a class="elsevierStyleCrossRef" href="#bib0325"><span class="elsevierStyleSup">25</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">Resultados conflitantes s&#227;o observados entre as variantes do gene MBL2 e a suscetibilidade &#224; leishmaniose&#46; Variantes&#44; caracterizando altos n&#237;veis da prote&#237;na&#44; foram associadas &#224; suscetibilidade &#224; LV na &#193;frica&#44;<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">26</span></a> no nordeste do Brasil<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">27</span></a> e na &#205;ndia&#46;<a class="elsevierStyleCrossRef" href="#bib0340"><span class="elsevierStyleSup">28</span></a> No entanto&#44; um estudo realizado em indiv&#237;duos com CL no norte do Amazonas mostrou que todos os polimorfismos relacionados a baixos n&#237;veis de MBL tiveram uma forte associa&#231;&#227;o com a susceptibilidade&#46;<a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">29</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">Alguns estudos foram conduzidos anteriormente para avaliar os efeitos dos polimorfismos do gene MBL2 no progresso da infec&#231;&#227;o em leishmaniose&#44; com resultados contradit&#243;rios&#44; em virtude do pequeno tamanho de amostra&#44; que carece de poder adequado para detectar os efeitos dos polimorfismos do gene <span class="elsevierStyleItalic">MBL2</span> na leishmaniose&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">At&#233; o momento&#44; nenhuma revis&#227;o sistem&#225;tica foi realizada com variantes do gene <span class="elsevierStyleItalic">MBL2</span> e leishmaniose&#46; O uso da metan&#225;lise como ferramenta estat&#237;stica que explora os fatores de risco associados a diferentes doen&#231;as gen&#233;ticas pode fornecer uma conclus&#227;o confi&#225;vel&#46; Esta revis&#227;o sistem&#225;tica incluiu estudos de caso&#8208;controle de associa&#231;&#227;o gen&#233;tica de variantes &#40;rs11003125&#44; rs7096206&#44; rs7095891&#44; rs5030737&#44; rs1800450 e rs1800451&#41; no gene <span class="elsevierStyleItalic">MBL2</span> e risco de desenvolver leishmaniose&#46; Esta revis&#227;o sistem&#225;tica est&#225; no registro internacional prospectivo de revis&#245;es sistem&#225;ticas &#40;PROSPERO&#41;&#58; CRD42020201755&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Materiais e m&#233;todos</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Pesquisa de banco de dados</span><p id="par0040" class="elsevierStylePara elsevierViewall">Esta revis&#227;o sistem&#225;tica foi conduzida de acordo com as recomenda&#231;&#245;es do protocolo PRISMA &#40;<span class="elsevierStyleItalic">Preferred Reporting Items for Systematic reviews and Meta&#8208;Analyzes</span>&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0350"><span class="elsevierStyleSup">30</span></a> PubMed&#44; Science Direct&#44; Cochrane Library&#44; Scopus e Lilacs foram pesquisados at&#233; dezembro de 2019 por tr&#234;s revisores independentes&#44; sem restri&#231;&#227;o de idioma ou tempo&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">Foi usada a estrat&#233;gia&#58; P<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>pacientes sob risco de leishmaniose&#59; I<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>presen&#231;a de polimorfismos&#59; C<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>aus&#234;ncia de polimorfismos&#59; O<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>ocorr&#234;ncia de leishmaniose&#46; Os seguintes termos de pesquisa foram usados&#58; &#40;&#8220;Leishmaniasis&#8221; OR &#8220;Cutaneous Leishmaniasis&#8221; OR &#8220;Visceral Leishmaniasis&#8221; OR &#8220;Leishmania Infection&#8221; OR &#8220;Leishmania Infections&#8221;&#41; AND &#40;&#8220;Mannose&#8208;binding Lectin&#8221; OR &#8220;Mannose&#8208;binding Lectin 2&#8221; OR &#8220;MBL&#8221; OR &#8220;MBL2&#8221;&#41; AND &#40;&#8220;Polymorphism&#8221; OR &#8220;Polymorphisms&#8221; OR &#8220;Single Nucleotide Polymorphism&#8221; OR &#8220;Single Nucleotide Polymorphisms&#8221;&#41;&#46; As refer&#234;ncias citadas em artigos eleg&#237;veis foram pesquisadas manualmente para identificar publica&#231;&#245;es adicionais&#46; A aprova&#231;&#227;o &#233;tica e o consentimento informado n&#227;o foram necess&#225;rios&#44; uma vez que este estudo foi baseado em estudos publicados anteriormente e n&#227;o teve contato direto com o paciente ou influ&#234;ncias no atendimento ao paciente&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Sele&#231;&#227;o de estudos</span><p id="par0050" class="elsevierStylePara elsevierViewall">Dois pesquisadores avaliaram independentemente todos os resultados da pesquisa&#46; Os crit&#233;rios de inclus&#227;o foram os seguintes&#58; 1&#41; estudo caso&#8208;controle&#44; 2&#41; rs11003125 &#40;&#8208;550&#41;&#44; rs7096206 &#40;&#8208;221&#41;&#44; rs7095891 &#40;&#43;4&#41;&#44; rs5030737 &#40;c&#243;don 52&#41;&#44; rs1800450 &#40;CD54&#41; e rs1800451 &#40;CD57&#41; polimorfismos&#44; 3&#41; estudos com dados de genotipagem suficientemente dispon&#237;veis para o c&#225;lculo dos <span class="elsevierStyleItalic">Odds Ratios</span> &#40;OR&#41; com Intervalos de Confian&#231;a de 95&#37; &#40;95&#37; IC&#41; e 4&#41; o Equil&#237;brio de Hardy&#8208;Weinberg &#40;HWE&#41;&#46; Os crit&#233;rios de exclus&#227;o foram&#58; 1&#41; estudo n&#227;o caso&#8208;controle&#44; 2&#41; relatos de caso&#44; 3&#41; revis&#245;es&#44; 4&#41; estudos em animais&#44; 5&#41; editoriais&#44; 6&#41; estudos sem dados dispon&#237;veis&#44; 7&#41; estudos com metan&#225;lise&#44; 8&#41; outros polimorfismos e 9&#41; dados duplicados&#46; Posteriormente&#44; todos os artigos selecionados foram checados por um terceiro pesquisador&#44; que resolveu as diverg&#234;ncias&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Extra&#231;&#227;o de dados</span><p id="par0055" class="elsevierStylePara elsevierViewall">Dois pesquisadores extra&#237;ram independentemente os seguintes dados dos estudos inclu&#237;dos&#58; ano de publica&#231;&#227;o&#44; primeiro autor&#44; regi&#227;o do estudo&#44; grupo &#233;tnico&#44; forma cl&#237;nica&#44; n&#250;mero de amostras&#44; idade e SNPs estudados&#46; As diverg&#234;ncias entre os pesquisadores foram discutidas e resolvidas pela consulta a um terceiro pesquisador&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Avalia&#231;&#227;o de pontua&#231;&#227;o de qualidade</span><p id="par0060" class="elsevierStylePara elsevierViewall">A escala <span class="elsevierStyleItalic">Newcastle&#8208;Ottawa</span> &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">tabela 1</a>&#41; foi usada para avaliar a qualidade dos estudos eleg&#237;veis&#46; Usando esse sistema&#44; cada estudo inclu&#237;do foi submetido a tr&#234;s julgamentos&#58; 1&#41; sele&#231;&#227;o de grupos de estudo&#59; 2&#41; comparabilidade dos grupos e 3&#41; resultado de interesse &#40;caso&#8208;controle&#41;&#46; Tr&#234;s pesquisadores calcularam independentemente a pontua&#231;&#227;o de cada publica&#231;&#227;o&#46; Os escores variaram de 0 a 9&#46; Os estudos com escore<span class="elsevierStyleHsp" style=""></span>&#62; 6 foram considerados de alta qualidade&#44; enquanto escore &#60; 6&#44; de baixa qualidade&#46; As diverg&#234;ncias entre os pesquisadores foram discutidas em grupo e resolvidas em consenso&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">An&#225;lise estat&#237;stica</span><p id="par0065" class="elsevierStylePara elsevierViewall">A metan&#225;lise avaliou a associa&#231;&#227;o do gene MBL2 e leishmaniose sob o modelo gen&#233;tico al&#233;lico&#44; &#8208;550 &#40;H <span class="elsevierStyleItalic">vs</span>&#46; L&#41;&#44; &#8208;221 &#40;X <span class="elsevierStyleItalic">vs</span>&#46; Y&#41;&#44; &#43;4 &#40;Q <span class="elsevierStyleItalic">vs</span>&#46; P&#41;&#44; CD52 &#40;A <span class="elsevierStyleItalic">vs</span>&#46; D&#41;&#44; CD54 &#40;A <span class="elsevierStyleItalic">vs</span>&#46; B&#41;&#44; CD57 &#40;A <span class="elsevierStyleItalic">vs</span>&#46; C&#41; e gen&#243;tipo A&#47;O &#40;A <span class="elsevierStyleItalic">vs</span>&#46; O&#41;&#46; O I<span class="elsevierStyleSup">2</span> foi utilizado para avaliar a heterogeneidade entre os estudos onde os valores 25&#37;&#44; 50&#37; e 75&#37; corresponderam a baixa&#44; moderada e alta heterogeneidade&#44; respectivamente&#46; O modelo fixo foi usado quando I<span class="elsevierStyleSup">2</span> &#60;<span class="elsevierStyleHsp" style=""></span>50&#37;&#44; e o modelo aleat&#243;rio foi usado quando I<span class="elsevierStyleSup">2</span><span class="elsevierStyleHsp" style=""></span>&#62; 50&#37;&#46; OR agrupados foram calculados usando o Mantel&#8208;Haenszel&#44; e a signific&#226;ncia estat&#237;stica de OR foi determinada usando estat&#237;stica Z&#46; Em ambos os modelos&#44; o valor p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;005 foi considerado estatisticamente significativo&#46; O <span class="elsevierStyleItalic">software</span> RStudio &#40;<a href="http://www.rstudio.com/products/rstudio/">www&#46;rstudio&#46;com&#47;products&#47;rstudio&#47;</a>&#41;&#44; vers&#227;o 1&#46;3&#46;1 para Windows foi usado como programa estat&#237;stico para o estudo&#46; Pacotes &#40;&#8220;<span class="elsevierStyleItalic">tidyverse</span>&#8221;&#41;&#44; &#40;&#8220;meta&#8221;&#41;&#44; &#40;&#8220;<span class="elsevierStyleItalic">metafor</span>&#8221;&#41;&#46;</p></span></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Resultados</span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Caracter&#237;sticas dos estudos inclu&#237;dos</span><p id="par0070" class="elsevierStylePara elsevierViewall">Foram pulicados 389 artigos identificados usando as bases de dados da literatura cient&#237;fica &#40;<a class="elsevierStyleCrossRef" href="#fig0005">fig&#46; 1</a>&#41;&#46; Dentre os artigos selecionados&#44; 35 foram removidos por duplica&#231;&#227;o&#44; 349 artigos foram exclu&#237;dos por n&#227;o atenderem aos crit&#233;rios de inclus&#227;o&#46; Por fim&#44; apenas quatro artigos&#44;<a class="elsevierStyleCrossRefs" href="#bib0330"><span class="elsevierStyleSup">26&#8211;29</span></a> respeitando os crit&#233;rios obrigat&#243;rios&#44; foram inclu&#237;dos na metan&#225;lise&#46; Esses estudos foram publicados em ingl&#234;s entre 2007 e 2015 &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">tabela 2</a>&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0075" class="elsevierStylePara elsevierViewall">Um estudo foi realizado em crian&#231;as africanas&#46;<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">26</span></a> Outros dois estudos foram de popula&#231;&#245;es mistas do Nordeste do Brasil&#44; compostas por 21&#37; de europeus&#44; 31&#37; de africanos e 48&#37; de ancestrais nativos americanos&#44;<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">27</span></a> e do norte do Brasil &#40;estado do Amazonas&#41;&#44; com uma popula&#231;&#227;o mista de 10&#37; de africanos&#44; 40&#37; ancestrais europeus e 50&#37; dos nativos americanos&#46;<a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">29</span></a> O quarto estudo foi realizado na &#205;ndia&#44; mas n&#227;o especificou a etnia dos indiv&#237;duos estudados&#46;<a class="elsevierStyleCrossRef" href="#bib0340"><span class="elsevierStyleSup">28</span></a> Tr&#234;s estudos analisaram pacientes com LV<a class="elsevierStyleCrossRefs" href="#bib0330"><span class="elsevierStyleSup">26&#8211;28</span></a> e um analisou pacientes com CL&#46;<a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">29</span></a><span class="elsevierStyleItalic">Leishmania</span> spp&#46; identificadas foram&#58; <span class="elsevierStyleItalic">L&#46; chagasi</span>&#44;<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">27</span></a><span class="elsevierStyleItalic">L&#46; infantum</span>&#44;<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">26</span></a><span class="elsevierStyleItalic">L&#46; guyanensis</span><a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">29</span></a> e <span class="elsevierStyleItalic">L&#46; donovani</span>&#46;<a class="elsevierStyleCrossRef" href="#bib0340"><span class="elsevierStyleSup">28</span></a> Um estudo analisou todos os polimorfismos alvo desta metan&#225;lise&#44;<a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">29</span></a> enquanto outro apenas cinco SNPs &#40;rs11003125&#44; rs7096206&#44; rs5030737&#44; rs1800450 e rs1800451&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">27</span></a> Um estudo analisou tr&#234;s SNPs &#40;rs7096206&#44; rs1800450 e rs1800451&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">26</span></a> e o estudo restante apenas um SNP &#40;rs7095891&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0340"><span class="elsevierStyleSup">28</span></a> Dois estudos forneceram dados suficientes para realizar a an&#225;lise do sistema A&#47;O&#46;<a class="elsevierStyleCrossRefs" href="#bib0335"><span class="elsevierStyleSup">27&#44;29</span></a> Um total de 1&#46;758 pessoas participaram desses estudos &#40;791 pacientes e 967 controles&#41;&#46; De acordo com a escala de Newcastle&#8208;Ottawa&#44; dois estudos obtiveram 9 pontos e dois com 8 pontos &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">tabela 1</a>&#41;&#46; A frequ&#234;ncia dos gen&#243;tipos e alelos est&#227;o organizados na <a class="elsevierStyleCrossRef" href="#tbl0015">tabela 3</a>&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Metan&#225;lise</span><p id="par0080" class="elsevierStylePara elsevierViewall">Os resultados da metan&#225;lise s&#227;o mostrados na <a class="elsevierStyleCrossRef" href="#fig0010">figura 2</a>&#46; Nenhuma das an&#225;lises para qualquer modelo gen&#233;tico de alelo para as duas variantes &#40;&#8208;550 e &#8208;221&#41; no promotor e as variantes &#43;4 na regi&#227;o n&#227;o traduzida mostraram associa&#231;&#227;o com suscetibilidade ou resist&#234;ncia &#224; leishmaniose &#40;o alelo &#8208;550H&#58; OR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;92&#59; 95&#37; IC<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;76&#8208;1&#44;12&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;93&#59; I<span class="elsevierStyleSup">2</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#37; e alelo &#8208;550L&#58; OR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#44;08&#59; 95&#37; IC<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;89&#8208;1&#44;32&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;93&#59; I<span class="elsevierStyleSup">2</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#37;&#41;&#44; o alelo &#8208;221X&#58; OR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;98&#59; 95&#37; IC<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;45&#8208;2&#44;13&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;01&#59; I<span class="elsevierStyleSup">2</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>91&#37; e alelo &#8208;221Y&#58; OR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#44;02&#59; 95&#37; IC<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;47&#8208;2&#44;22&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;01&#59; I<span class="elsevierStyleSup">2</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>91&#37;&#41; e o alelo Q &#43;4&#58; OR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;85&#59; 95&#37; IC<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;54&#8208;1&#44;33&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;03&#59; I<span class="elsevierStyleSup">2</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>79&#37; e alelo P&#58; OR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#44;17&#59; 95&#37; IC<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;75&#8208;1&#44;84&#59;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;03&#59; I<span class="elsevierStyleSup">2</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>79&#37;&#41;&#46; Resultados semelhantes foram obtidos para variantes localizadas no exon 1 CD52 &#40;alelo A do alelo&#58; OR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#44;13&#59; 95&#37; IC<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;68&#8208;1&#44;87&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;87&#59; I<span class="elsevierStyleSup">2</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#37; e alelo D do alelo&#58; OR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;89&#59; 95&#37; IC<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;53&#8208;1&#44;47&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;87&#59; I<span class="elsevierStyleSup">2</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#37;&#41;&#44; CD54 &#40;alelo A&#58; OR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#44;04&#59; 95&#37; IC<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;62&#8208;1&#44;75&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;01&#59; I<span class="elsevierStyleSup">2</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>79&#37; e alelo B&#58; OR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;96&#59; 95&#37; IC<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;57&#8208;1&#44;61&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;01&#59; I<span class="elsevierStyleSup">2</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>79&#37;&#41; e CD57 &#40;alelo A&#58; OR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;85&#59; 95&#37; IC<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;44&#8208;1&#44;62&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;03&#59; I<span class="elsevierStyleSup">2</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>72&#37; e alelo C&#58; OR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#44;18&#59; 95&#37; IC<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;62&#8208;2&#44;26&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;03&#59; I<span class="elsevierStyleSup">2</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>72&#37;&#41;&#46; A presen&#231;a do alelo A selvagem &#40;alelo A&#58; OR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#44;05&#59; 95&#37; IC<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;39&#8208;2&#44;81&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;01&#59; I<span class="elsevierStyleSup">2</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>94&#37;&#41; e alelo O mutante &#40;alelo O&#58; OR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;95&#59; 95&#37; IC<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;36&#8208;2&#44;56&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;01&#59; I<span class="elsevierStyleSup">2</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>94&#37;&#41; tamb&#233;m n&#227;o foram associados &#224; suscetibilidade ou resist&#234;ncia&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia></span></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Discuss&#227;o</span><p id="par0085" class="elsevierStylePara elsevierViewall">A MBL reconhece a presen&#231;a de manose na superf&#237;cie dos pat&#243;genos para promover a opsoniza&#231;&#227;o e a ativa&#231;&#227;o do sistema complemento&#46;<a class="elsevierStyleCrossRef" href="#bib0355"><span class="elsevierStyleSup">31</span></a> A MBL desempenha papel fundamental na resposta imune inata&#44;<a class="elsevierStyleCrossRef" href="#bib0360"><span class="elsevierStyleSup">32</span></a> destacando sua concentra&#231;&#227;o s&#233;rica como requisito para a predisposi&#231;&#227;o ao desenvolvimento de doen&#231;as infecciosas humanas&#46;<a class="elsevierStyleCrossRefs" href="#bib0365"><span class="elsevierStyleSup">33&#44;34</span></a> As variantes do gene <span class="elsevierStyleItalic">MBL2</span> foram associadas a risco aumentado de infec&#231;&#227;o por protozo&#225;rios&#46;<a class="elsevierStyleCrossRefs" href="#bib0375"><span class="elsevierStyleSup">35&#44;36</span></a> No entanto&#44; poucos estudos investigaram variantes gen&#233;ticas no gene <span class="elsevierStyleItalic">MBL2</span> na infec&#231;&#227;o por leishmania&#46;<a class="elsevierStyleCrossRefs" href="#bib0330"><span class="elsevierStyleSup">26&#8211;29</span></a> Tr&#234;s estudos sugeriram que as variantes correlacionadas com baixos n&#237;veis circulantes de MBL s&#227;o protetoras para VL&#44;<a class="elsevierStyleCrossRefs" href="#bib0330"><span class="elsevierStyleSup">26&#44;28</span></a> enquanto um estudo mostrou suscetibilidade ao CL&#46;<a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">29</span></a></p><p id="par0090" class="elsevierStylePara elsevierViewall">Os resultados conflitantes gerados pela maioria dos estudos tiveram um poder estat&#237;stico fraco em virtude do pequeno tamanho da amostra inclu&#237;da&#46; Para esclarecer resultados contradit&#243;rios em estudos de associa&#231;&#227;o gen&#233;tica&#44; a metan&#225;lise oferece um m&#233;todo poderoso para sintetizar dados obtidos de estudos independentes&#46;<a class="elsevierStyleCrossRef" href="#bib0385"><span class="elsevierStyleSup">37</span></a> Para abordar as limita&#231;&#245;es dos estudos de caso&#8208;controle&#44; a presente metan&#225;lise foi realizada para fornecer evid&#234;ncias estat&#237;sticas da associa&#231;&#227;o entre os polimorfismos do gene <span class="elsevierStyleItalic">MBL2</span> e a suscetibilidade &#224; leishmaniose com ORs agrupados&#46; At&#233; o momento&#44; esta &#233; a primeira metan&#225;lise que aborda a associa&#231;&#227;o entre os polimorfismos descritos e a leishmaniose&#46; Metan&#225;lises anteriores sugeriram uma associa&#231;&#227;o de polimorfismos nos genes IL2RA &#40;receptor alfa da interleucina 2&#41;<a class="elsevierStyleCrossRef" href="#bib0390"><span class="elsevierStyleSup">38</span></a> e SLC11A1 &#40;fam&#237;lia transportadora de soluto 11 <span class="elsevierStyleItalic">member</span> a1&#41;<a class="elsevierStyleCrossRef" href="#bib0395"><span class="elsevierStyleSup">39</span></a> com os aspectos cl&#237;nicos da leishmaniose&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">Neste estudo&#44; os dados de quatro artigos foram analisados de acordo com os alelos de baixa e alta produ&#231;&#227;o da MBL&#46; No entanto&#44; as an&#225;lises de metan&#225;lise n&#227;o mostraram associa&#231;&#227;o entre os alelos do gene <span class="elsevierStyleItalic">MBL2</span> e a suscetibilidade &#224; leishmaniose &#40;<a class="elsevierStyleCrossRef" href="#fig0005">fig&#46; 1</a>&#41;&#46; Alta heterogenicidade foi observada para as variantes&#58; &#8208;550 H&#47;L &#40;91&#37;&#41;&#44; &#43;4 Q&#47;P &#40;79&#37;&#41;&#44; CD54 A&#47;B &#40;79&#37;&#41;&#44; CD57 A&#47;C &#40;72&#37;&#41; e A&#47;O &#40;94&#37;&#41;&#46; Isso pode ser explicado principalmente pelo fato de haver miscigena&#231;&#227;o &#233;tnica nos indiv&#237;duos dos estudos selecionados&#46; Tr&#234;s estudos investigaram pacientes com VL&#44;<a class="elsevierStyleCrossRefs" href="#bib0330"><span class="elsevierStyleSup">26&#8211;28</span></a> e um paciente investigado com LC&#46;<a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">29</span></a> Em cada estudo&#44; a esp&#233;cie do agente etiol&#243;gico foi diferente&#46; &#201; importante notar que o valor da heterogeneidade influencia o modelo estat&#237;stico adequado&#46; Estudos com pequenos tamanhos de amostra podem mostrar resultados n&#227;o confi&#225;veis&#46; Como consequ&#234;ncia&#44; o modelo aleat&#243;rio deve ser sempre aplicado&#46;<a class="elsevierStyleCrossRef" href="#bib0400"><span class="elsevierStyleSup">40</span></a> Dentre os estudos selecionados&#44; um analisou todos os seis polimorfismos alvo&#44; os dipl&#243;tipos&#44; e tamb&#233;m os hapl&#243;tipos&#44;<a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">29</span></a> com um n&#250;mero amostral elevado&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">No entanto&#44; deve&#8208;se ter cautela na interpreta&#231;&#227;o desses resultados&#44; pois se baseiam em poucos estudos&#44; os quais apresentam resultados divergentes quando analisados separadamente&#46; Portanto&#44; mais estudos s&#227;o necess&#225;rios para confirmar se as variantes que determinam os n&#237;veis s&#233;ricos baixos s&#227;o suscet&#237;veis ou protetoras&#46; Ressaltamos a import&#226;ncia do estudo de associa&#231;&#227;o envolvendo marcadores gen&#233;ticos na leishmaniose&#44; para novos entendimentos sobre os mecanismos moleculares da doen&#231;a&#46; As variantes podem ser utilizadas como marcadores moleculares da predisposi&#231;&#227;o do indiv&#237;duo a certos tipos de doen&#231;as ou como alvos terap&#234;uticos no desenvolvimento de novos medicamentos&#46;</p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Conclus&#227;o</span><p id="par0105" class="elsevierStylePara elsevierViewall">Esta metan&#225;lise n&#227;o mostrou associa&#231;&#227;o significativa entre os polimorfismos rs11003125&#44; rs7096206&#44; rs7095891&#44; rs5030737&#44; rs1800450 e rs1800451 do gene <span class="elsevierStyleItalic">MBL2</span> e leishmaniose&#46;</p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Suporte financeiro</span><p id="par0110" class="elsevierStylePara elsevierViewall">Nenhum&#46;</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Contribui&#231;&#227;o dos autores</span><p id="par0115" class="elsevierStylePara elsevierViewall">Wonei de Seixas Vital&#58; Conceitua&#231;&#227;o&#59; an&#225;lise formal&#59; metodologia&#59; supervis&#227;o&#59; valida&#231;&#227;o&#59; reda&#231;&#227;o &#8211; revis&#227;o e edi&#231;&#227;o&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">Felipe Jules de Ara&#250;jo Santos&#58; Conceitua&#231;&#227;o&#59; an&#225;lise formal&#59; metodologia&#59; supervis&#227;o&#59; valida&#231;&#227;o&#59; reda&#231;&#227;o &#8211; revis&#227;o e edi&#231;&#227;o&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">Maur&#237;cio Leandro Fernandes Gon&#231;alves&#58; Curadoria de dados&#59; an&#225;lise formal&#59; metodologia&#59; reda&#231;&#227;o &#8211; rascunho original&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">Claudia Dantas Comandolli Wyrepkowski&#58; Curadoria de dados&#59; an&#225;lise formal&#59; metodologia&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">Rajendranath Ramasawmy&#58; Curadoria de dados&#59; an&#225;lise formal&#59; metodologia&#59; reda&#231;&#227;o&#59; revis&#227;o final&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">Silvania da Concei&#231;&#227;o Furtado&#58; Conceitua&#231;&#227;o&#59; an&#225;lise formal&#59; metodologia&#59; supervis&#227;o&#59; valida&#231;&#227;o&#59; reda&#231;&#227;o &#8211; revis&#227;o e edi&#231;&#227;o&#46;</p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Conflito de interesses</span><p id="par0145" class="elsevierStylePara elsevierViewall">Nenhum&#46;</p></span></span>"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Fundamentos</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">A leishmaniose &#233; causada por um protozo&#225;rio intracelular do g&#234;nero <span class="elsevierStyleItalic">Leishmania</span>&#46; Lectina ligante de manose &#40;MBL&#41; &#233; uma prote&#237;na do complemento do soro e reconhece ant&#237;genos lipoproteicos nos protozo&#225;rios e na membrana plasm&#225;tica da bact&#233;ria&#46; Variantes de nucleot&#237;deos na regi&#227;o promotora e &#233;xon 1 do gene <span class="elsevierStyleItalic">MBL</span> podem influenciar sua express&#227;o ou alterar sua estrutura molecular&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Objetivo</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Avaliar por meio de revis&#227;o sistem&#225;tica estudos de caso&#8208;controle de associa&#231;&#227;o gen&#233;tica de variantes no gene <span class="elsevierStyleItalic">MBL2</span> e o risco de desenvolver leishmaniose&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">M&#233;todos</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Esta revis&#227;o pesquisou os bancos de dados PubMed&#44; Science Direct&#44; Cochrane Library&#44; Scopus e Lilacs para publica&#231;&#245;es de caso&#8208;controle com seis polimorfismos no gene lectina ligante de manose&#46; Foi usada a estrat&#233;gia&#58; P<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>pacientes sob risco de leishmaniose&#59; I<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>presen&#231;a de polimorfismos&#59; C<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>aus&#234;ncia de polimorfismos&#59; O<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>ocorr&#234;ncia de leishmaniose&#46; Quatro estudos de caso&#47;controle consistindo em 791 pacientes com leishmaniose e 967 indiv&#237;duos saud&#225;veis &#40;controle&#41; est&#227;o inclu&#237;dos nesta metan&#225;lise&#46; A associa&#231;&#227;o de variantes no gene lectina ligante de manose e leishmaniose sob o modelo gen&#233;tico al&#233;lico&#44; &#8208;550 &#40;H <span class="elsevierStyleItalic">vs</span>&#46; L&#41;&#44; &#8208;221 &#40;X <span class="elsevierStyleItalic">vs</span>&#46; Y&#41;&#44; &#43;4 &#40;Q <span class="elsevierStyleItalic">vs</span>&#46; P&#41;&#44; CD52 &#40;A <span class="elsevierStyleItalic">vs</span>&#46; D&#41;&#44; CD54 &#40;A <span class="elsevierStyleItalic">vs</span>&#46; B&#41;&#44; CD57 &#40;A <span class="elsevierStyleItalic">vs</span>&#46; C&#41; e gen&#243;tipo A&#47;O &#40;A <span class="elsevierStyleItalic">vs</span>&#46; O&#41; foi avaliado&#46; Registro Internacional Prospectivo de Revis&#245;es Sistem&#225;ticas &#40;PROSPERO&#41;&#58; CRD42020201755&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Resultados</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Os resultados da metan&#225;lise para qualquer modelo gen&#233;tico al&#233;lico n&#227;o mostraram associa&#231;&#227;o significativa para as variantes dentro do promotor&#44; a regi&#227;o n&#227;o traduzida e o &#233;xon 1&#44; bem como para o alelo selvagem A e alelo mutante O com a leishmaniose&#46;</p></span> <span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Limita&#231;&#245;es do estudo</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Deve&#8208;se ter cautela ao interpretar esses resultados&#44; pois se baseiam em poucos estudos&#44; os quais apresentam resultados divergentes quando analisados separadamente&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Conclus&#245;es</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Esta metan&#225;lise n&#227;o mostrou associa&#231;&#227;o significativa entre os polimorfismos rs11003125&#44; rs7096206&#44; rs7095891&#44; rs5030737&#44; rs1800450 e rs1800451 do gene lectina ligante de manose e leishmaniose em qualquer avalia&#231;&#227;o al&#233;lica e heterog&#234;nea&#46;</p></span>"
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                  \t\t\t\t" scope="col">Estudo&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Representatividade&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Sele&#231;&#227;o de n&#227;o corte&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Pontua&#231;&#227;o final n&#227;o presente no in&#237;cio&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Total&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Felipe FJ&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">&#42;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">9&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Salsabil H&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">&#42;&#42;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">&#42;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">9&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">Alonso DP&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">&#42;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">&#42;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">&#42;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">&#42;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">&#42;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">&#42;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Anshuman M&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#42;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#42;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#42;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#42;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#42;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#42;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#42;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#42;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab2929230.png"
              ]
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          ]
        ]
        "descripcion" => array:1 [
          "pt" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Escala de Newcastle&#8208;Ottawa dos estudos inclu&#237;dos</p>"
        ]
      ]
      3 => array:8 [
        "identificador" => "tbl0010"
        "etiqueta" => "Tabela 2"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at2"
            "detalle" => "Tabela "
            "rol" => "short"
          ]
        ]
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">NR&#44; n&#227;o relatado&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Ano&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Estudo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Pa&#237;s&#47; Regi&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Grupo &#233;tnico&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Formas cl&#237;nicas&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="2" align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Amostras caso controle</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="2" align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Idade&#44; m&#233;dia de anos<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>DP ou m&#233;dia &#40;intervalo&#41; caso controle</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">SNPs&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2007&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Alonso DP&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Brasil&#47; Nordeste&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Misto&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">LV&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">61&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">231&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6 meses a 73 anos&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6 meses a 73 anos&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">rs11003125&#44; rs7096206&#44; rs5030737&#44; rs1800450&#44; rs1800451&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2015&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">De Ara&#250;jo FJ&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Brasil&#47; Norte&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Misto&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">LC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">400&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">382&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">311 homens &#40;32<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>15&#44;5 anos&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">225 homens &#40;38<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>17&#44;6 anos&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">rs11003125&#44; rs7096206&#44; rs7095891&#44; rs5030737&#44; rs1800450&#44; rs1800451&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">89 mulheres &#40;32<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>13&#44;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">157 mulheres &#40;34<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>17&#44;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2013&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Salsabil H&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Marrocos &#47; Norte&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Africana&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">LV&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">112&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">139&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>12 anos&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8&#44;5<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>12 anos&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">rs7096206&#44; rs1800450&#44; rs1800451&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2015&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Anshuman M&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#205;ndia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">LV&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">218&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">215&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">28&#44;7<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>16&#44;7 anos&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">35&#46;3<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>16&#44;2 anos&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">rs7095891&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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              "imagenFichero" => array:1 [
                0 => "xTab2929229.png"
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        "descripcion" => array:1 [
          "pt" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Leishmaniose&#46; Caracter&#237;sticas dos estudos inclu&#237;dos na revis&#227;o sistem&#225;tica</p>"
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Total sample&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">HH&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">LL&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">HL&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">L&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Alonso DP&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2007&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">60&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">226&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4 &#40;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">29 &#40;48&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">27 &#40;45&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">37 &#40;31&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">83 &#40;69&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">25 &#40;11&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">99 &#40;44&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">102 &#40;45&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">149 &#40;33&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">303 &#40;67&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">de Ara&#250;jo FJ&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">2015&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">365&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">332&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">49 &#40;13&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">167 &#40;46&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">149 &#40;41&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">265 &#40;36&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">465 &#40;64&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">53 &#40;16&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">147 &#40;44&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">132 &#40;40&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">253 &#40;38&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">411 &#40;62&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleBold">&#8208;221</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleBold">XX</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleBold">XY</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleBold">YY</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">X</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleBold">Y</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">XX</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">XY</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">YY</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">X</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">Y</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Alonso DP&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2007&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">60&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">226&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0 &#40;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">14 &#40;23&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">46 &#40;77&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Salsabiln H&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2013&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">139&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">71 &#40;51&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">167 &#40;60&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">de Ara&#250;jo FJ&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">2015&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">365&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">332&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">30 &#40;08&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">563 &#40;85&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleBold">&#43;4</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleBold">QQ</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleBold">QP</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleBold">PP</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleBold">Q</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleBold">P</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleBold">QQ</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleBold">QP</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleBold">P</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">de Ara&#250;jo FJ&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2015&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">365&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">332&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">17 &#40;5&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">95 &#40;26&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">253 &#40;69&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">129 &#40;18&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">601 &#40;82&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">9 &#40;3&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">94 &#40;28&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">229 &#40;69&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">111 &#40;17&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">551 &#40;83&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Anshuman M&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">2015&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">218&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">215&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">96 &#40;22&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">340 &#40;78&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Alonso DP&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">2007&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Salsabiln H&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">2013&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">de Ara&#250;jo FJ&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">2015&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">Alonso DP&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">2007&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">Salsabiln H&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">2013&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">Alonso DP&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">2007&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">de Ara&#250;jo FJ&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">2015&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">155 &#40;42&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">84 &#40;23&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">153 &#40;46&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">439 &#40;66&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">225 &#40;34&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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              "imagenFichero" => array:1 [
                0 => "xTab2929228.png"
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        "descripcion" => array:1 [
          "pt" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Modelo gen&#233;tico al&#233;lico adotado na metan&#225;lise para avaliar a associa&#231;&#227;o de polimorfismos do gene <span class="elsevierStyleItalic">MBL2</span> e leishmaniose</p>"
        ]
      ]
    ]
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      "titulo" => "Refer&#234;ncias"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0015"
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            0 => array:3 [
              "identificador" => "bib0205"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:1 [
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "E&#46; Torres-Guerrero"
                            1 => "M&#46;R&#46; Quintanilla-Cedillo"
                            2 => "J&#46; Ruiz-Esmenjaud"
                            3 => "R&#46; Arenas"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:4 [
                        "tituloSerie" => "Leishmaniose&#58; a review&#46;"
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                        "volumen" => "6"
                        "paginaInicial" => "750"
                      ]
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                ]
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            1 => array:3 [
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              "etiqueta" => "2"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Worldwide risk factors in leishmaniasis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "A&#46; Oryan"
                            1 => "M&#46; Akbari"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.apjtm.2016.06.021"
                      "Revista" => array:6 [
                        "tituloSerie" => "Asian Pacific Journal of Tropical Medicine&#46;"
                        "fecha" => "2016"
                        "volumen" => "9"
                        "paginaInicial" => "925"
                        "paginaFinal" => "932"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27794384"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            2 => array:3 [
              "identificador" => "bib0215"
              "etiqueta" => "3"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Leishmaniasis worldwide and global estimates of its incidence"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "J&#46; Alvar"
                            1 => "I&#46;D&#46; V&#233;lez"
                            2 => "C&#46; Bern"
                            3 => "M&#46; Herrero"
                            4 => "P&#46; Desjeux"
                            5 => "J&#46; Cano"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1371/journal.pone.0035671"
                      "Revista" => array:5 [
                        "tituloSerie" => "PLoS One&#46;"
                        "fecha" => "2012"
                        "volumen" => "7"
                        "paginaInicial" => "e35671"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22693548"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
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                ]
              ]
            ]
            3 => array:3 [
              "identificador" => "bib0220"
              "etiqueta" => "4"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:1 [
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "S&#46; Burza"
                            1 => "S&#46;L&#46; Croft"
                            2 => "M&#46; Boelaert"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Leishmaniose&#46; Lancet"
                        "fecha" => "2018"
                        "volumen" => "392"
                        "paginaInicial" => "951"
                        "paginaFinal" => "970"
                      ]
                    ]
                  ]
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              "identificador" => "bib0225"
              "etiqueta" => "5"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Human genetics of leishmania infections"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
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Journal Information
Vol. 97. Issue 3.
Pages 298-306 (1 May 2022)
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5277
Vol. 97. Issue 3.
Pages 298-306 (1 May 2022)
Artigo original
Open Access
A influência da presença de polimorfismos de lectina ligante de manose na ocorrência da leishmaniose: revisão sistemática e metanálise
Visits
5277
Wonei de Seixas Vitala,
Corresponding author
wonei.vital@pucpr.edu.br

Autor para correspondência.
, Felipe Jules de Araújo Santosb, Maurício Leandro Fernandes Gonçalvesc, Claudia Dantas Comandolli Wyrepkowskid, Rajendranath Ramasawmyb, Silvania da Conceição Furtadoe
a Pontifícia Universidade Católica do Paraná, Curitiba, PR, Brasil
b Fundação de Medicina Tropical Dr. Heitor Vieira Dourado, Manaus, AM, Brasil
c Universidade Estácio de Sá, Manaus, AM, Brasil
d Instituto Nacional de Pesquisas da Amazônia, Manaus, AM, Brasil
e Departamento de Morfologia, Universidade Federal do Amazonas, Manaus, AM, Brasil
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Abstract
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Figures (2)
Tables (3)
Tabela 1. Escala de Newcastle‐Ottawa dos estudos incluídos
Tabela 2. Leishmaniose. Características dos estudos incluídos na revisão sistemática
Tabela 3. Modelo genético alélico adotado na metanálise para avaliar a associação de polimorfismos do gene MBL2 e leishmaniose
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Resumo
Fundamentos

A leishmaniose é causada por um protozoário intracelular do gênero Leishmania. Lectina ligante de manose (MBL) é uma proteína do complemento do soro e reconhece antígenos lipoproteicos nos protozoários e na membrana plasmática da bactéria. Variantes de nucleotídeos na região promotora e éxon 1 do gene MBL podem influenciar sua expressão ou alterar sua estrutura molecular.

Objetivo

Avaliar por meio de revisão sistemática estudos de caso‐controle de associação genética de variantes no gene MBL2 e o risco de desenvolver leishmaniose.

Métodos

Esta revisão pesquisou os bancos de dados PubMed, Science Direct, Cochrane Library, Scopus e Lilacs para publicações de caso‐controle com seis polimorfismos no gene lectina ligante de manose. Foi usada a estratégia: P=pacientes sob risco de leishmaniose; I=presença de polimorfismos; C=ausência de polimorfismos; O=ocorrência de leishmaniose. Quatro estudos de caso/controle consistindo em 791 pacientes com leishmaniose e 967 indivíduos saudáveis (controle) estão incluídos nesta metanálise. A associação de variantes no gene lectina ligante de manose e leishmaniose sob o modelo genético alélico, ‐550 (H vs. L), ‐221 (X vs. Y), +4 (Q vs. P), CD52 (A vs. D), CD54 (A vs. B), CD57 (A vs. C) e genótipo A/O (A vs. O) foi avaliado. Registro Internacional Prospectivo de Revisões Sistemáticas (PROSPERO): CRD42020201755.

Resultados

Os resultados da metanálise para qualquer modelo genético alélico não mostraram associação significativa para as variantes dentro do promotor, a região não traduzida e o éxon 1, bem como para o alelo selvagem A e alelo mutante O com a leishmaniose.

Limitações do estudo

Deve‐se ter cautela ao interpretar esses resultados, pois se baseiam em poucos estudos, os quais apresentam resultados divergentes quando analisados separadamente.

Conclusões

Esta metanálise não mostrou associação significativa entre os polimorfismos rs11003125, rs7096206, rs7095891, rs5030737, rs1800450 e rs1800451 do gene lectina ligante de manose e leishmaniose em qualquer avaliação alélica e heterogênea.

Palavras‐chave:
Lectina de ligação a Manose
Leishmaniose
Polimorfismo genético
Full Text
Introdução

A leishmaniose, uma doença transmitida através da picada da fêmea de um inseto hematófago da família dos flebótomos, causada por protozoários parasitas intracelulares pertencentes ao gênero Leishmania.1 A leishmaniose exibe uma variedade de características clínicas, como leishmaniose cutânea (LC), leishmaniose mucocutânea (LM) e leishmaniose visceral (LV).2 Doze milhões de pessoas em 98 países são vítimas de leishmaniose. Aproximadamente, 1,5 a 2,0 milhões e 500.000 novos casos de CL e LV, respectivamente, são observados anualmente. A leishmaniose causa cerca de 40 mil mortes por ano3 e é influenciada por diversos fatores, como origem genética do hospedeiro, aspectos nutricionais, Leishmania spp., meio ambiente e aspecto imunológico.4 Um estudo recente relatou que as variações genéticas do hospedeiro podem desempenhar papel fundamental na suscetibilidade à leishmaniose.5 Muitos genes foram investigados, evidenciando forte relação entre SNPs e risco de desenvolver leishmaniose, incluindo interferon‐gama (IFN‐G)6 e interleucina‐6 (IL‐6).7

A lectina de ligação à manose (MBL) é um receptor de reconhecimento de patógenos (PRR) e desempenha papel crítico na imunidade do hospedeiro. A MBL leva à ativação do sistema complemento.8,9 Essa proteína oligomérica consiste em subunidades estruturais formadas por três polipeptídios idênticos de 32 kD, cada um contendo uma ligação cruzada com a região N‐terminal da cisteína, colágeno ligado à região do pescoço e uma região do domínio C‐terminal que reconhece carboidratos em microrganismos.10

Por meio de múltiplos domínios da lectina, carboidratos como manose (carboidratos de seis carbonos) são encontrados na superfície de vários patógenos, incluindo Trypanosoma cruzi,11Plasmodium falciparum12 e Mycobacterium tuberculosis.13 Após o reconhecimento dessas moléculas pela lectina, as serina proteases são ativadas para facilitar a opsonização (fagocitose) pelos macrófagos e a lise da superfície do microrganismo.14 A forma infecciosa da leishmania (promastigota) é caracterizada pela presença de lipofosfoglicanos (GLP) e outras moléculas como a manose.15,16 Esses componentes atuam como padrões moleculares associados a patógenos (PAMPs) que são reconhecidos pelos componentes do complemento.17,18

O gene MBL2 está localizado no cromossomo 10 (10q11.2‐q21).19 Nesse gene, vários SNPs foram identificados, os quais são conhecidos por seu efeito funcional que influencia o desenvolvimento de doenças infecciosas.20–22 Os SNPs funcionais, localizados na região do promotor, como o SNP ‐550 H/L (substituição de G> C, rs11003125), ‐221 X/Y (substituição de C> G, rs7096206) e +4 Q/P (A substituição de C> T, rs7095891) localizada na região não traduzida, pode regular a taxa de transcrição do gene.23 No primeiro éxon existem três SNPs localizados no códon 52 CGT> TGT (rs5030737), códon 54 GGC> GAC (rs1800450) e códon 57 GGA> GAA (rs1800451), correspondendo a alterações de aminoácidos entre arginina para cisteína (Arg52Cys, alelo D), glicina para ácido aspártico (Gly54Asp, alelo B) e glicina para ácido glutâmico (Gly57Glu, alelo C) na região colágena da cadeia polipeptídica, respectivamente.24 Esses três polimorfismos formam o sistema AO, no qual o alelo selvagem é descrito como o alelo A, e o alelo O como um mutante. O genótipo A/O está correlacionado com baixos níveis da proteína e indetectável para o genótipo O/O.25

Resultados conflitantes são observados entre as variantes do gene MBL2 e a suscetibilidade à leishmaniose. Variantes, caracterizando altos níveis da proteína, foram associadas à suscetibilidade à LV na África,26 no nordeste do Brasil27 e na Índia.28 No entanto, um estudo realizado em indivíduos com CL no norte do Amazonas mostrou que todos os polimorfismos relacionados a baixos níveis de MBL tiveram uma forte associação com a susceptibilidade.29

Alguns estudos foram conduzidos anteriormente para avaliar os efeitos dos polimorfismos do gene MBL2 no progresso da infecção em leishmaniose, com resultados contraditórios, em virtude do pequeno tamanho de amostra, que carece de poder adequado para detectar os efeitos dos polimorfismos do gene MBL2 na leishmaniose.

Até o momento, nenhuma revisão sistemática foi realizada com variantes do gene MBL2 e leishmaniose. O uso da metanálise como ferramenta estatística que explora os fatores de risco associados a diferentes doenças genéticas pode fornecer uma conclusão confiável. Esta revisão sistemática incluiu estudos de caso‐controle de associação genética de variantes (rs11003125, rs7096206, rs7095891, rs5030737, rs1800450 e rs1800451) no gene MBL2 e risco de desenvolver leishmaniose. Esta revisão sistemática está no registro internacional prospectivo de revisões sistemáticas (PROSPERO): CRD42020201755.

Materiais e métodosPesquisa de banco de dados

Esta revisão sistemática foi conduzida de acordo com as recomendações do protocolo PRISMA (Preferred Reporting Items for Systematic reviews and Meta‐Analyzes).30 PubMed, Science Direct, Cochrane Library, Scopus e Lilacs foram pesquisados até dezembro de 2019 por três revisores independentes, sem restrição de idioma ou tempo.

Foi usada a estratégia: P=pacientes sob risco de leishmaniose; I=presença de polimorfismos; C=ausência de polimorfismos; O=ocorrência de leishmaniose. Os seguintes termos de pesquisa foram usados: (“Leishmaniasis” OR “Cutaneous Leishmaniasis” OR “Visceral Leishmaniasis” OR “Leishmania Infection” OR “Leishmania Infections”) AND (“Mannose‐binding Lectin” OR “Mannose‐binding Lectin 2” OR “MBL” OR “MBL2”) AND (“Polymorphism” OR “Polymorphisms” OR “Single Nucleotide Polymorphism” OR “Single Nucleotide Polymorphisms”). As referências citadas em artigos elegíveis foram pesquisadas manualmente para identificar publicações adicionais. A aprovação ética e o consentimento informado não foram necessários, uma vez que este estudo foi baseado em estudos publicados anteriormente e não teve contato direto com o paciente ou influências no atendimento ao paciente.

Seleção de estudos

Dois pesquisadores avaliaram independentemente todos os resultados da pesquisa. Os critérios de inclusão foram os seguintes: 1) estudo caso‐controle, 2) rs11003125 (‐550), rs7096206 (‐221), rs7095891 (+4), rs5030737 (códon 52), rs1800450 (CD54) e rs1800451 (CD57) polimorfismos, 3) estudos com dados de genotipagem suficientemente disponíveis para o cálculo dos Odds Ratios (OR) com Intervalos de Confiança de 95% (95% IC) e 4) o Equilíbrio de Hardy‐Weinberg (HWE). Os critérios de exclusão foram: 1) estudo não caso‐controle, 2) relatos de caso, 3) revisões, 4) estudos em animais, 5) editoriais, 6) estudos sem dados disponíveis, 7) estudos com metanálise, 8) outros polimorfismos e 9) dados duplicados. Posteriormente, todos os artigos selecionados foram checados por um terceiro pesquisador, que resolveu as divergências.

Extração de dados

Dois pesquisadores extraíram independentemente os seguintes dados dos estudos incluídos: ano de publicação, primeiro autor, região do estudo, grupo étnico, forma clínica, número de amostras, idade e SNPs estudados. As divergências entre os pesquisadores foram discutidas e resolvidas pela consulta a um terceiro pesquisador.

Avaliação de pontuação de qualidade

A escala Newcastle‐Ottawa (tabela 1) foi usada para avaliar a qualidade dos estudos elegíveis. Usando esse sistema, cada estudo incluído foi submetido a três julgamentos: 1) seleção de grupos de estudo; 2) comparabilidade dos grupos e 3) resultado de interesse (caso‐controle). Três pesquisadores calcularam independentemente a pontuação de cada publicação. Os escores variaram de 0 a 9. Os estudos com escore> 6 foram considerados de alta qualidade, enquanto escore < 6, de baixa qualidade. As divergências entre os pesquisadores foram discutidas em grupo e resolvidas em consenso.

Tabela 1.

Escala de Newcastle‐Ottawa dos estudos incluídos

Estudo  SeleçãoComparabilidadeResultado
  Representatividade  Seleção de não corte  Investigação  Pontuação final não presente no início  Comparabilidade (confusão)  Avaliação de resultados  Duração/ Rastreio  Monitoramento de adequação  Total 
Felipe FJ  ** 
Salsabil H  ** 
Alonso DP 
Anshuman M 

Cada item foi pontuado com pontuação máxima de um ponto (um *), com exceção da comparabilidade, que permitia dois pontos.

Análise estatística

A metanálise avaliou a associação do gene MBL2 e leishmaniose sob o modelo genético alélico, ‐550 (H vs. L), ‐221 (X vs. Y), +4 (Q vs. P), CD52 (A vs. D), CD54 (A vs. B), CD57 (A vs. C) e genótipo A/O (A vs. O). O I2 foi utilizado para avaliar a heterogeneidade entre os estudos onde os valores 25%, 50% e 75% corresponderam a baixa, moderada e alta heterogeneidade, respectivamente. O modelo fixo foi usado quando I2 <50%, e o modelo aleatório foi usado quando I2> 50%. OR agrupados foram calculados usando o Mantel‐Haenszel, e a significância estatística de OR foi determinada usando estatística Z. Em ambos os modelos, o valor p=0,005 foi considerado estatisticamente significativo. O software RStudio (www.rstudio.com/products/rstudio/), versão 1.3.1 para Windows foi usado como programa estatístico para o estudo. Pacotes (“tidyverse”), (“meta”), (“metafor”).

ResultadosCaracterísticas dos estudos incluídos

Foram pulicados 389 artigos identificados usando as bases de dados da literatura científica (fig. 1). Dentre os artigos selecionados, 35 foram removidos por duplicação, 349 artigos foram excluídos por não atenderem aos critérios de inclusão. Por fim, apenas quatro artigos,26–29 respeitando os critérios obrigatórios, foram incluídos na metanálise. Esses estudos foram publicados em inglês entre 2007 e 2015 (tabela 2).

Figura 1.

Fluxograma do processo de revisão da literatura de acordo com o protocolo PRISMA.

(0.25MB).
Tabela 2.

Leishmaniose. Características dos estudos incluídos na revisão sistemática

Ano  Estudo  País/ Região  Grupo étnico  Formas clínicas  Amostras caso controleIdade, média de anos±DP ou média (intervalo) caso controleSNPs 
2007  Alonso DP  Brasil/ Nordeste  Misto  LV  61  231  6 meses a 73 anos  6 meses a 73 anos  rs11003125, rs7096206, rs5030737, rs1800450, rs1800451 
2015  De Araújo FJ  Brasil/ Norte  Misto  LC  400  382  311 homens (32±15,5 anos)  225 homens (38±17,6 anos)  rs11003125, rs7096206, rs7095891, rs5030737, rs1800450, rs1800451 
              89 mulheres (32±13,7)  157 mulheres (34±17,5)   
2013  Salsabil H  Marrocos / Norte  Africana  LV  112  139  7±12 anos  8,5±12 anos  rs7096206, rs1800450, rs1800451 
2015  Anshuman M  Índia  NR  LV  218  215  28,7±16,7 anos  35.3±16,2 anos  rs7095891 

NR, não relatado.

Um estudo foi realizado em crianças africanas.26 Outros dois estudos foram de populações mistas do Nordeste do Brasil, compostas por 21% de europeus, 31% de africanos e 48% de ancestrais nativos americanos,27 e do norte do Brasil (estado do Amazonas), com uma população mista de 10% de africanos, 40% ancestrais europeus e 50% dos nativos americanos.29 O quarto estudo foi realizado na Índia, mas não especificou a etnia dos indivíduos estudados.28 Três estudos analisaram pacientes com LV26–28 e um analisou pacientes com CL.29Leishmania spp. identificadas foram: L. chagasi,27L. infantum,26L. guyanensis29 e L. donovani.28 Um estudo analisou todos os polimorfismos alvo desta metanálise,29 enquanto outro apenas cinco SNPs (rs11003125, rs7096206, rs5030737, rs1800450 e rs1800451).27 Um estudo analisou três SNPs (rs7096206, rs1800450 e rs1800451),26 e o estudo restante apenas um SNP (rs7095891).28 Dois estudos forneceram dados suficientes para realizar a análise do sistema A/O.27,29 Um total de 1.758 pessoas participaram desses estudos (791 pacientes e 967 controles). De acordo com a escala de Newcastle‐Ottawa, dois estudos obtiveram 9 pontos e dois com 8 pontos (tabela 1). A frequência dos genótipos e alelos estão organizados na tabela 3.

Tabela 3.

Modelo genético alélico adotado na metanálise para avaliar a associação de polimorfismos do gene MBL2 e leishmaniose

Estudo  Ano  Total sample    CasoControle
‐550        HH  HL  LL  HH  HL  LL 
Alonso DP  2007  60  226  4 (7)  29 (48)  27 (45)  37 (31)  83 (69)  25 (11)  99 (44)  102 (45)  149 (33)  303 (67) 
de Araújo FJ  2015  365  332  49 (13)  167 (46)  149 (41)  265 (36)  465 (64)  53 (16)  147 (44)  132 (40)  253 (38)  411 (62) 
‐221        XX  XY  YY  X  Y  XX  XY  YY  X  Y 
Alonso DP  2007  60  226  0 (0)  14 (23)  46 (77)  14 (12)  106 (88)  4 (2)  64 (28)  158 (70)  72 (16)  380 (84) 
Salsabiln H  2013  112  139  15 (13)  39 (34)  58 (52)  69 (31)  155 (69)  20 (14)  71 (51)  48 (35)  111 (40)  167 (60) 
de Araújo FJ  2015  365  332  30 (08)  125 (34)  210 (58)  185 (25)  545 (75)  12 (4)  77 (23)  243 (73)  101 (15)  563 (85) 
+4        QQ  QP  PP  Q  P  QQ  QP  PP  Q  P 
de Araújo FJ  2015  365  332  17 (5)  95 (26)  253 (69)  129 (18)  601 (82)  9 (3)  94 (28)  229 (69)  111 (17)  551 (83) 
Anshuman M  2015  218  215  12 (6)  72 (33)  134 (61)  96 (22)  340 (78)  22 (10)  83 (39)  110 (51)  127 (29)  303 (71) 
CD52        AA  AD  DD  A  D  AA  AD  DD  A  D 
Alonso DP  2007  61  231  58 (95)  3 (5)  0 (0)  119 (98)  3 (2)  218 (94)  12 (5.1)  1 (0.9)  448 (97)  14 (3) 
de Araújo FJ  2015  366  332  342 (93)  22 (6)  2 (1)  706 (96)  26 (04)  306 (92)  26 (8)  0 (0)  638 (96)  26 (4) 
CD54        AA  AB  BB  A  B  AA  AB  BB  A  B 
Alonso DP  2007  61  231  41 (67)  19 (31)  1 (2)  101 (83)  21 (17)  117 (51)  96 (41)  18 (8)  330 (71)  132 (29) 
Salsabiln H  2013  104  133  71 (68)  27 (26)  6 (6)  169 (81)  39 (19)  96 (72)  32 (24)  5 (4)  224 (84)  42 (16) 
de Araújo FJ  2015  366  332  215 (59)  121 (33)  30 (8)  551 (75)  181 (25)  211 (63)  105 (32)  16 (5)  527 (79)  137 (21) 
CD57        AA  AC  CC  A  C  AA  AC  CC  A  C 
Alonso DP  2007  61  231  55 (90)  6 (10)  0 (0)  116 (95)  6 (5)  202 (87)  28 (12)  1 (1)  432 (94)  30 (6) 
Salsabiln H  2013  104  133  88 (85)  15 (14)  1 (1)  176 (91)  17 (9)  111 (83)  18 (14)  4 (3)  240 (90)  26 (10) 
de Araújo FJ  2015  365  332  255 (70)  91 (25)  19 (5)  601 (82)  129 (18)  270 (81)  57 (17)  5 (2)  597 (90)  67 (10) 
A/O        AA  AO  OO  A  O  AA  AO  OO  A  O 
Alonso DP  2007  61  231  36 (59)  20 (33)  5 (8)  92 (75)  30 (25)  95 (41)  103 (45)  33 (14)  293 (63)  169 (37) 
de Araújo FJ  2015  365  332  126 (35)  155 (42)  84 (23)  407 (56)  323 (44)  153 (46)  133 (40)  46 (14)  439 (66)  225 (34) 
Metanálise

Os resultados da metanálise são mostrados na figura 2. Nenhuma das análises para qualquer modelo genético de alelo para as duas variantes (‐550 e ‐221) no promotor e as variantes +4 na região não traduzida mostraram associação com suscetibilidade ou resistência à leishmaniose (o alelo ‐550H: OR=0,92; 95% IC=0,76‐1,12; p=0,93; I2=0% e alelo ‐550L: OR=1,08; 95% IC=0,89‐1,32; p=0,93; I2=0%), o alelo ‐221X: OR=0,98; 95% IC=0,45‐2,13; p=0,01; I2=91% e alelo ‐221Y: OR=1,02; 95% IC=0,47‐2,22; p=0,01; I2=91%) e o alelo Q +4: OR=0,85; 95% IC=0,54‐1,33; p=0,03; I2=79% e alelo P: OR=1,17; 95% IC=0,75‐1,84;p=0,03; I2=79%). Resultados semelhantes foram obtidos para variantes localizadas no exon 1 CD52 (alelo A do alelo: OR=1,13; 95% IC=0,68‐1,87; p=0,87; I2=0% e alelo D do alelo: OR=0,89; 95% IC=0,53‐1,47; p=0,87; I2=0%), CD54 (alelo A: OR=1,04; 95% IC=0,62‐1,75; p=0,01; I2=79% e alelo B: OR=0,96; 95% IC=0,57‐1,61; p=0,01; I2=79%) e CD57 (alelo A: OR=0,85; 95% IC=0,44‐1,62; p=0,03; I2=72% e alelo C: OR=1,18; 95% IC=0,62‐2,26; p=0,03; I2=72%). A presença do alelo A selvagem (alelo A: OR=1,05; 95% IC=0,39‐2,81; p=0,01; I2=94%) e alelo O mutante (alelo O: OR=0,95; 95% IC=0,36‐2,56; p=0,01; I2=94%) também não foram associados à suscetibilidade ou resistência.

Figura 2.

Forestplot de meta‐análise da comparação entre alelos mutantes versus alelos de tipo selvagem dos SNPs.

(1.49MB).
Discussão

A MBL reconhece a presença de manose na superfície dos patógenos para promover a opsonização e a ativação do sistema complemento.31 A MBL desempenha papel fundamental na resposta imune inata,32 destacando sua concentração sérica como requisito para a predisposição ao desenvolvimento de doenças infecciosas humanas.33,34 As variantes do gene MBL2 foram associadas a risco aumentado de infecção por protozoários.35,36 No entanto, poucos estudos investigaram variantes genéticas no gene MBL2 na infecção por leishmania.26–29 Três estudos sugeriram que as variantes correlacionadas com baixos níveis circulantes de MBL são protetoras para VL,26,28 enquanto um estudo mostrou suscetibilidade ao CL.29

Os resultados conflitantes gerados pela maioria dos estudos tiveram um poder estatístico fraco em virtude do pequeno tamanho da amostra incluída. Para esclarecer resultados contraditórios em estudos de associação genética, a metanálise oferece um método poderoso para sintetizar dados obtidos de estudos independentes.37 Para abordar as limitações dos estudos de caso‐controle, a presente metanálise foi realizada para fornecer evidências estatísticas da associação entre os polimorfismos do gene MBL2 e a suscetibilidade à leishmaniose com ORs agrupados. Até o momento, esta é a primeira metanálise que aborda a associação entre os polimorfismos descritos e a leishmaniose. Metanálises anteriores sugeriram uma associação de polimorfismos nos genes IL2RA (receptor alfa da interleucina 2)38 e SLC11A1 (família transportadora de soluto 11 member a1)39 com os aspectos clínicos da leishmaniose.

Neste estudo, os dados de quatro artigos foram analisados de acordo com os alelos de baixa e alta produção da MBL. No entanto, as análises de metanálise não mostraram associação entre os alelos do gene MBL2 e a suscetibilidade à leishmaniose (fig. 1). Alta heterogenicidade foi observada para as variantes: ‐550 H/L (91%), +4 Q/P (79%), CD54 A/B (79%), CD57 A/C (72%) e A/O (94%). Isso pode ser explicado principalmente pelo fato de haver miscigenação étnica nos indivíduos dos estudos selecionados. Três estudos investigaram pacientes com VL,26–28 e um paciente investigado com LC.29 Em cada estudo, a espécie do agente etiológico foi diferente. É importante notar que o valor da heterogeneidade influencia o modelo estatístico adequado. Estudos com pequenos tamanhos de amostra podem mostrar resultados não confiáveis. Como consequência, o modelo aleatório deve ser sempre aplicado.40 Dentre os estudos selecionados, um analisou todos os seis polimorfismos alvo, os diplótipos, e também os haplótipos,29 com um número amostral elevado.

No entanto, deve‐se ter cautela na interpretação desses resultados, pois se baseiam em poucos estudos, os quais apresentam resultados divergentes quando analisados separadamente. Portanto, mais estudos são necessários para confirmar se as variantes que determinam os níveis séricos baixos são suscetíveis ou protetoras. Ressaltamos a importância do estudo de associação envolvendo marcadores genéticos na leishmaniose, para novos entendimentos sobre os mecanismos moleculares da doença. As variantes podem ser utilizadas como marcadores moleculares da predisposição do indivíduo a certos tipos de doenças ou como alvos terapêuticos no desenvolvimento de novos medicamentos.

Conclusão

Esta metanálise não mostrou associação significativa entre os polimorfismos rs11003125, rs7096206, rs7095891, rs5030737, rs1800450 e rs1800451 do gene MBL2 e leishmaniose.

Suporte financeiro

Nenhum.

Contribuição dos autores

Wonei de Seixas Vital: Conceituação; análise formal; metodologia; supervisão; validação; redação – revisão e edição.

Felipe Jules de Araújo Santos: Conceituação; análise formal; metodologia; supervisão; validação; redação – revisão e edição.

Maurício Leandro Fernandes Gonçalves: Curadoria de dados; análise formal; metodologia; redação – rascunho original.

Claudia Dantas Comandolli Wyrepkowski: Curadoria de dados; análise formal; metodologia.

Rajendranath Ramasawmy: Curadoria de dados; análise formal; metodologia; redação; revisão final.

Silvania da Conceição Furtado: Conceituação; análise formal; metodologia; supervisão; validação; redação – revisão e edição.

Conflito de interesses

Nenhum.

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Como citar este artigo: Vital WS, Santos FJA, Gonçalves MLF, Wyrepkowski CDC, Ramasawmy R, Furtado SC. Influence of the presence of mannose‐binding lectin polymorphisms on the occurrence of leishmaniasis: a systematic review and meta‐analysis. An Bras Dermatol. 2022;97:298–306.

Trabalho realizado na Universidade Federal do Amazonas, Manaus, AM, Brasil.

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