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unhas ou articula&#231;&#245;es pode ser observado em at&#233; 50&#37; dos pacientes&#46; A associa&#231;&#227;o da psor&#237;ase com v&#225;rios dist&#250;rbios sist&#234;micos&#44; como doen&#231;as cardiovasculares&#44; infec&#231;&#245;es&#44; dist&#250;rbios metab&#243;licos&#44; doen&#231;as renais&#44; doen&#231;as gastrintestinais e c&#226;ncer&#44; est&#225; bem documentada&#46;<a class="elsevierStyleCrossRefs" href="#bib0220"><span class="elsevierStyleSup">3&#8211;5</span></a> A etiopatog&#234;nese da doen&#231;a ainda n&#227;o est&#225; bem esclarecida&#46; A psor&#237;ase &#233; classificada como uma doen&#231;a multifatorial&#59; fatores gen&#233;ticos&#44; ambientais&#44; imunol&#243;gicos e inflamat&#243;rios contribuem para sua patog&#234;nese&#46;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">6</span></a> Inflama&#231;&#227;o&#44; tanto lesional quanto sist&#234;mica&#44; &#233; uma caracter&#237;stica importante da psor&#237;ase&#46; Muitos estudos que avaliaram a inflama&#231;&#227;o sist&#234;mica na psor&#237;ase apontaram que marcadores de inflama&#231;&#227;o &#40;especialmente prote&#237;na C&#8208;reativa&#44; fator de necrose tumoral &#91;TNF&#93;&#8208;&#945;&#44; mol&#233;cula de ades&#227;o intercelular &#91;ICAM&#93;&#8208;1&#44; E&#8208;selectina e interleucinas &#91;IL&#93;&#8208;1&#946;&#44; IL &#8208;6&#44; IL&#8208;10&#41; est&#227;o aumentados em pacientes psori&#225;sicos&#44; criam um estado inflamat&#243;rio sist&#234;mico que pode levar a comorbidades como doen&#231;as cardiovasculares&#46;<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">7</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">As enzimas do citocromo P450 &#40;CYP&#41; s&#227;o hemoprote&#237;nas localizadas principalmente no ret&#237;culo endoplasm&#225;tico &#40;RE&#41; ou na membrana mitocondrial em humanos&#46; A principal fun&#231;&#227;o dos CYPs &#233; metabolizar medicamentos&#44; xenobi&#243;ticos n&#227;o medicamentosos e endobi&#243;ticos&#44; como &#225;cidos graxos&#44; esteroides e horm&#244;nios esteroides&#44; &#225;cidos biliares&#44; vitamina D&#44; prostaglandinas e &#225;cido araquid&#244;nico &#40;AA&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0245"><span class="elsevierStyleSup">8&#8211;10</span></a> O AA &#233; metabolizado em quatro &#225;cidos epoxieicosatrienoicos &#40;EETs&#41; 5&#44;6&#8208;EET&#44; 8&#44;9&#8208;EET&#44; 11&#44;12&#8208;EET e 14&#44;15&#8208;EET&#46; Os EETs promovem relaxamento vascular&#44; t&#234;m efeito anti&#8208;inflamat&#243;rio no endot&#233;lio e efeito cardioprotetor durante eventos isqu&#234;micos&#46;<a class="elsevierStyleCrossRefs" href="#bib0260"><span class="elsevierStyleSup">11&#44;12</span></a> Al&#233;m de seu efeito favor&#225;vel sobre doen&#231;as cardiovasculares e inflamat&#243;rias&#44; os EETs tamb&#233;m podem promover prolifera&#231;&#227;o&#44; migra&#231;&#227;o e sobreviv&#234;ncia nas c&#233;lulas tumorais&#46;<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">13</span></a> O CYP2J2 &#40;isoforma do CYP&#44; expresso principalmente no f&#237;gado&#44; 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94 pacientes com psor&#237;ase diagnosticada cl&#237;nica ou histopatologicamente foram admitidos no Hospital de Pesquisa e Treinamento Ankara Numune entre janeiro de 2015 e julho de 2016&#46; Como grupo controle&#44; foram recrutados 100 pacientes pareados por sexo e idade admitidos no ambulat&#243;rio de dermatologia&#44; com uma doen&#231;a dermatol&#243;gica que n&#227;o psor&#237;ase e sem hist&#243;rico de doen&#231;a inflamat&#243;ria cr&#244;nica&#46; As caracter&#237;sticas demogr&#225;ficas e cl&#237;nicas &#40;subtipo da doen&#231;a&#44; dura&#231;&#227;o&#44; gravidade&#44; hist&#243;rico familiar&#44; tratamentos&#44; hist&#243;rico de artrite psori&#225;sica e comprometimento de localiza&#231;&#227;o especial&#44; como couro cabeludo&#44; &#225;reas flexurais e unhas&#41; dos pacientes com psor&#237;ase e do grupo controle foram registradas&#46; A artrite psori&#225;sica foi avaliada em todos os pacientes&#46; O hist&#243;rico de artrite psori&#225;sica foi coletado&#59; os pacientes com artralgia ou artrite ativa foram encaminhados ao departamento de reumatologia para um diagn&#243;stico definitivo de artrite psori&#225;sica&#46; Pacientes com idade<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>18&#44; participantes gr&#225;vidas ou lactantes e participantes com hist&#243;rico de doen&#231;as imunol&#243;gicas ou inflamat&#243;rias foram exclu&#237;dos do estudo&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">O estudo foi aprovado pelo comit&#234; de &#233;tica local &#40;E&#8208;15&#8208;612&#41; e todos os participantes assinaram um termo de consentimento livre e esclarecido antes do estudo&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">An&#225;lise do polimorfismo</span><p id="par0030" class="elsevierStylePara elsevierViewall">O desenho do <span class="elsevierStyleItalic">primer</span> foi feito para a amplifica&#231;&#227;o por rea&#231;&#227;o em cadeia da polimerase &#40;PCR&#41; da regi&#227;o do polimorfismo CYP2J2 &#8208;50G<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>T&#44; de modo que o local do polimorfismo estivesse a 150<span class="elsevierStyleHsp" style=""></span>bp de ambas as extremidades do <span class="elsevierStyleItalic">amplicon</span> de PCR&#46; Isso foi necess&#225;rio porque foi usado um kit de sequenciamento que faz a leitura a 150 pb das duas extremidades&#46; Antes de pedirem os <span class="elsevierStyleItalic">primers</span>&#44; os autores adicionaram sequ&#234;ncias espec&#237;ficas de cerca de 30 nucleot&#237;dios &#224;s extremidades 5&#8217; dos <span class="elsevierStyleItalic">primers</span>&#44; para tornar os <span class="elsevierStyleItalic">amplicons</span> adequados para o sequenciamento indexado nas plataformas Illumina&#46; A <a class="elsevierStyleCrossRef" href="#tbl0005">tabela 1</a> resume os pares de <span class="elsevierStyleItalic">primers</span> de PCR&#44; as sequ&#234;ncias espec&#237;ficas de <span class="elsevierStyleItalic">locus</span> e as sequ&#234;ncias adicionadas para a PCR &#237;ndice&#46; As amostras de DNA foram obtidas isolando&#8208;se 200<span class="elsevierStyleHsp" style=""></span>&#956;L de amostras de sangue de cada participante&#44; com um QIAamp DNA Blood Mini Kit &#40;Qiagen Inc&#46;&#41;&#46; As PCRs foram feitas em amostras de DNA isoladas com os <span class="elsevierStyleItalic">primers</span> projetados&#59; as rea&#231;&#245;es foram verificadas usando eletroforese em gel de agarose a 2&#37;&#46; Uma segunda PCR para fins de indexa&#231;&#227;o foi feita para adicionar sequ&#234;ncias &#237;ndice aos <span class="elsevierStyleItalic">amplicons</span>&#44; para alcan&#231;ar a multiplexa&#231;&#227;o no sequenciamento de pr&#243;ximo gene&#46; Para cada uma das amostras&#44; foi usada uma combina&#231;&#227;o diferente de <span class="elsevierStyleItalic">primers</span> &#237;ndice&#46; As rea&#231;&#245;es de indexa&#231;&#227;o por PCR tamb&#233;m foram verificadas com eletroforese em gel de agarose a 2&#37;&#46; Volumes iguais de rea&#231;&#245;es de PCR indexadas foram misturados para obter um <span class="elsevierStyleItalic">pool</span> de PCR&#44; que inclu&#237;a todos os <span class="elsevierStyleItalic">amplicons</span> de todas as amostras&#46; O <span class="elsevierStyleItalic">pool</span> de PCR foi purificado com um kit NucleoFast&#174; 96&#160;PCR &#40;Macherey&#8208;Nagel GmbH&#41;&#46; O <span class="elsevierStyleItalic">pool</span> purificado foi quantificado com um espectrofot&#244;metro de microvolume e dilu&#237;do de acordo com as recomenda&#231;&#245;es da Illumina Inc&#46; O sequenciamento de segunda gera&#231;&#227;o das amostras foi feito com o sistema Miseq &#40;Illumina Inc&#46;&#41;&#46; A genotipagem das amostras foi finalizada quando os dados foram analisados no <span class="elsevierStyleItalic">software</span> IGV&#160;v&#46; 2&#46;3 &#40;Broad Institute&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">An&#225;lise estat&#237;stica</span><p id="par0035" class="elsevierStylePara elsevierViewall">O SPSS Statistics para Windows v&#46; 21&#46;0 &#40;IBM Corp&#46; &#8211; Armonk&#44; NY&#44; Estados Unidos&#41; foi usado para an&#225;lise estat&#237;stica&#46; As vari&#225;veis quantitativas foram analisadas com o teste qui&#8208;quadrado ou o teste exato de Fisher&#44; quando necess&#225;rio&#59; as vari&#225;veis qualitativas foram analisadas com o teste U de Mann&#8208;Whitney&#46; A correla&#231;&#227;o entre vari&#225;veis qualitativas foi avaliada pelo teste de correla&#231;&#227;o de Spearman&#46; Valores&#8208;p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;05 foram considerados como diferen&#231;as estatisticamente significativas em todas as an&#225;lises&#46;</p></span></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Resultados</span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Caracter&#237;sticas dos pacientes e caracter&#237;sticas cl&#237;nicas da psor&#237;ase</span><p id="par0040" class="elsevierStylePara elsevierViewall">As caracter&#237;sticas dos pacientes e os aspectos cl&#237;nicos da psor&#237;ase est&#227;o resumidos na <a class="elsevierStyleCrossRef" href="#tbl0005">tabela 1</a>&#46; Na distribui&#231;&#227;o por sexo&#44; 47&#37; dos pacientes eram do sexo masculino e 53&#37; do feminino&#46; A idade m&#233;dia dos pacientes foi de 44&#44;66 anos &#40;DP<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>12&#44;6&#41; e a idade m&#233;dia ao diagn&#243;stico de psor&#237;ase foi de 33&#44;21 anos &#40;DP<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>14&#44;9&#41;&#46; A idade dos pacientes e a idade ao diagn&#243;stico foram semelhantes nos pacientes do sexo masculino e feminino &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;39 e 0&#44;53&#44; respectivamente&#41;&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">O PASI m&#233;dio dos pacientes com psor&#237;ase foi 4&#44;51 &#40;DP<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>3&#44;86&#41;&#46; A psor&#237;ase vulgar &#40;PsV&#41; foi o tipo mais comum&#44; identificada em 76&#37; de todos os pacientes com psor&#237;ase&#46; A psor&#237;ase palmoplantar foi o segundo tipo mais comum &#40;11&#37;&#41;&#44; seguida pela gutata &#40;6&#37;&#41;&#44; eritrod&#233;rmica &#40;4&#37;&#41; e pustulosa &#40;3&#37;&#41;&#46; O comprometimento de pelo menos uma das localiza&#231;&#245;es especiais&#44; como couro cabeludo&#44; regi&#227;o flexural ou regi&#227;o genital&#44; foi observado em 74&#44;5&#37; dos pacientes com psor&#237;ase&#46; O couro cabeludo foi a localiza&#231;&#227;o especial mais frequentemente afetada&#46; Artralgia foi identificada em 47&#37; dos pacientes com psor&#237;ase e 23&#37; dos pacientes foram diagnosticados com artrite psori&#225;sica&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">Os tratamentos anteriores e atuais est&#227;o resumidos na <a class="elsevierStyleCrossRef" href="#tbl0010">tabela 2</a>&#46; Os esteroides t&#243;picos foram o tratamento anterior e atual mais comum em pacientes com psor&#237;ase &#40;99&#37; e 90&#37;&#44; respectivamente&#41;&#46; Entre os pacientes&#44; 23&#44;1&#37; apresentavam pelo menos uma doen&#231;a sist&#234;mica ou comorbidade associada&#46; Doen&#231;as cardiovasculares foram observadas em 11&#44;7&#37; dos pacientes&#44; e outras doen&#231;as sist&#234;micas em 22&#44;2&#37; &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">tabela 2</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">An&#225;lise do polimorfismo do gene CYP2J2</span><p id="par0055" class="elsevierStylePara elsevierViewall">A frequ&#234;ncia al&#233;lica e a distribui&#231;&#227;o do gen&#243;tipo do gene CYP2J2 em pacientes com psor&#237;ase e controles est&#227;o descritas na <a class="elsevierStyleCrossRef" href="#tbl0015">tabela 3</a>&#46; O alelo T e o gen&#243;tipo TT<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>GT no modelo dominante foram mais frequentes em pacientes com psor&#237;ase em compara&#231;&#227;o com os controles &#40;frequ&#234;ncia do alelo T 9&#44;04&#37; <span class="elsevierStyleItalic">vs</span>&#46; 4&#44;5&#37; e frequ&#234;ncia do gen&#243;tipo TT<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>GT 17&#44;02&#37; <span class="elsevierStyleItalic">vs</span>&#46; 8&#37;&#41;&#44; mas essa diferen&#231;a cl&#237;nica n&#227;o foi estatisticamente significativa &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;063 e p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;062&#44; respectivamente&#41;&#46; Os pacientes com psor&#237;ase foram divididos em dois subgrupos&#58; vulgar &#40;PsV&#41; e n&#227;o vulgar &#40;nVP&#41;&#46; A an&#225;lise de subgrupos mostrou que as frequ&#234;ncias do alelo T e do gen&#243;tipo TT<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>GT eram maiores em pacientes com PsV em compara&#231;&#227;o com o grupo controle &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;024 e p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;029&#44; respectivamente&#41;&#44; indicou que o polimorfismo do CYP2J2 estava associado a um aumento do risco de desenvolver PsV &#40;OR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>2&#44;82&#59; IC 95&#37;&#58;&#160;1&#44;11&#8208;7&#44;15&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;029&#41;&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0060" class="elsevierStylePara elsevierViewall">As caracter&#237;sticas demogr&#225;ficas e as caracter&#237;sticas da doen&#231;a de pacientes com psor&#237;ase com gen&#243;tipo GG &#40;tipo selvagem&#41; e gen&#243;tipo GT<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>TT &#40;polimorfismo homozigoto ou heterozigoto&#41; foram comparadas e resumidas na <a class="elsevierStyleCrossRef" href="#tbl0020">tabela 4</a>&#46; Embora o grupo polim&#243;rfico apresentasse mais pacientes com PsV do que pacientes com PsnV &#40;&#62; 2 vezes&#41;&#44; o resultado n&#227;o foi estatisticamente significativo &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;22&#41;&#46; A idade e o sexo dos pacientes&#44; idade ao in&#237;cio da doen&#231;a&#44; PASI&#44; presen&#231;a de comprometimento de localiza&#231;&#245;es especiais&#44; presen&#231;a de artralgia e artrite&#44; hist&#243;rico familiar positivo para psor&#237;ase&#44; presen&#231;a de doen&#231;as associadas e modalidades de tratamento foram semelhantes entre pacientes com psor&#237;ase com e sem polimorfismo&#46;</p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia></span></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Discuss&#227;o</span><p id="par0065" class="elsevierStylePara elsevierViewall">Este estudo investigou o poss&#237;vel papel do polimorfismo do CYP2J2 como fator de risco em pacientes com psor&#237;ase&#46; Os resultados demonstram uma frequ&#234;ncia significativamente mais alta do alelo T em pacientes com PsV e um risco aumentado de psor&#237;ase em pacientes com polimorfismo CYP2J2 no modelo dominante&#46; Tanto quanto &#233; do conhecimento dos autores&#44; este &#233; o primeiro estudo que investiga o papel do polimorfismo CYP2J2 na psor&#237;ase&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">O CYP2J2 50G<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>T &#233; um dos polimorfismos funcionais do CYP2J2 mais estudados&#46; Spiecker et al&#46; estudaram o efeito do polimorfismo CYP2J2 50G<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>T e observaram uma diminui&#231;&#227;o na liga&#231;&#227;o do fator de transcri&#231;&#227;o Sp1 ao DNA&#44; uma redu&#231;&#227;o na atividade do promotor e menores concentra&#231;&#245;es plasm&#225;ticas de EET em pacientes com polimorfismo G&#8208;50T em compara&#231;&#227;o com participantes com tipo selvagem&#46;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">19</span></a> EETs derivados do CYP2J2 induzem vasodilata&#231;&#227;o&#44; inibem inflama&#231;&#227;o&#44; apoptose e trombose e apresentam efeitos cardioprotetores&#46;<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">20</span></a> Ao alterar suas concentra&#231;&#245;es plasm&#225;ticas&#44; o polimorfismo do CYP pode afetar o papel cardioprotetor dos EETs e desempenhar um papel na patog&#234;nese das doen&#231;as cardiovasculares&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">O polimorfismo do CYP2J2 foi estudado principalmente em doen&#231;as cardiovasculares&#44; apresentou resultados contradit&#243;rios entre diferentes grupos &#233;tnicos&#46; Estudos que investigaram o polimorfismo CYP2J2 em doen&#231;as coronarianas revelaram um aumento do risco na popula&#231;&#227;o alem&#227;&#44; diminui&#231;&#227;o do risco em negros e nenhuma associa&#231;&#227;o em brancos e na popula&#231;&#227;o sueca&#46;<a class="elsevierStyleCrossRefs" href="#bib0295"><span class="elsevierStyleSup">18&#44;19&#44;21&#44;22</span></a> Polonikov et al&#46; evidenciaram um risco aumentado de hipertens&#227;o em pacientes russos&#59; no entanto&#44; essa associa&#231;&#227;o n&#227;o foi confirmada em negros ou brancos&#46;<a class="elsevierStyleCrossRefs" href="#bib0320"><span class="elsevierStyleSup">23&#8211;25</span></a> Polonikov et al&#46; tamb&#233;m descreveram uma rela&#231;&#227;o sexo&#8208;espec&#237;fica entre o polimorfismo do CYP2J2 e a hipertens&#227;o em pacientes russas do sexo feminino&#46;<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">26</span></a> N&#227;o foi identificada associa&#231;&#227;o significativa entre o polimorfismo CYP2J2 e acidente vascular cerebral nas popula&#231;&#245;es sueca e chinesa&#46;<a class="elsevierStyleCrossRefs" href="#bib0295"><span class="elsevierStyleSup">18&#44;27</span></a> Estudos recentes tamb&#233;m demonstraram que o CYP2J2 aumentou os n&#237;veis circulantes de EET e angiog&#234;nese induzida e melhorou a fun&#231;&#227;o card&#237;aca em ratos ap&#243;s infarto do mioc&#225;rdio&#46;<a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">28</span></a> As doen&#231;as cardiovasculares s&#227;o comorbidades frequentes e importantes na psor&#237;ase&#46; O presente estudo avaliou a associa&#231;&#227;o entre polimorfismo do CYP2J2 e comorbidades cardiovasculares&#46; N&#227;o foi observada uma associa&#231;&#227;o significativa entre o polimorfismo do CYP2J2 e a frequ&#234;ncia de comorbidade&#44; sugeriu&#8208;se que o CYP2J2 pode aumentar o risco do surgimento de PsV&#44; mas n&#227;o est&#225; associado a um risco aumentado de comorbidades cardiovasculares em pacientes com psor&#237;ase&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">Al&#233;m de seus efeitos cardiovasculares&#44; os EETs derivados do CYP2J2 tamb&#233;m modulam a inflama&#231;&#227;o&#46;<a class="elsevierStyleCrossRef" href="#bib0350"><span class="elsevierStyleSup">29</span></a> Node et al&#46; estudaram o efeito dos EETs derivados do CYP2J2 na inflama&#231;&#227;o vascular&#46; Seu estudo revelou que os EETs podem modular a resposta inflamat&#243;ria pela inibi&#231;&#227;o da express&#227;o induzida por citocinas pr&#243;&#8208;inflamat&#243;rias &#40;TNF&#8208;&#945;&#44; IL&#8208;1&#945; e lipopolissacar&#237;dio bacteriano&#41; das mol&#233;culas de ades&#227;o endotelial vascular &#40;VCAM&#8208;1&#44; ICAM&#8208;1 e E&#8208;selectin&#41; e diminuir o n&#250;mero de leuc&#243;citos mononucleares m&#243;veis&#47;aderentes&#46;<a class="elsevierStyleCrossRef" href="#bib0350"><span class="elsevierStyleSup">29</span></a> Os EETs tamb&#233;m apresentam efeitos anti&#8208;inflamat&#243;rios pela inibi&#231;&#227;o do fator nuclear kappaB &#40;NF&#8208;&#954;B&#41; e I&#954;B quinase&#44; ativa&#231;&#227;o dos receptores ativados pelo proliferador de peroxissoma&#44; aumento da express&#227;o da eNOS e regula&#231;&#227;o da homeostase do ret&#237;culo endoplasm&#225;tico&#46;<a class="elsevierStyleCrossRef" href="#bib0355"><span class="elsevierStyleSup">30</span></a></p><p id="par0085" class="elsevierStylePara elsevierViewall">Embora o efeito anti&#8208;inflamat&#243;rio dos EETs esteja bem documentado&#44; poucos estudos investigaram o polimorfismo do CYP2J2 em doen&#231;as inflamat&#243;rias&#46; Wang et al&#46; estudaram o polimorfismo do CYP2J2 em pacientes com diabetes <span class="elsevierStyleItalic">mellitus</span>&#46; Embora n&#227;o tenha sido observada diferen&#231;a significativa entre pacientes diab&#233;ticos e um grupo controle&#44; em pacientes diab&#233;ticos o polimorfismo do CYP2J2 demonstrou estar associado a menor idade de in&#237;cio&#46;<a class="elsevierStyleCrossRef" href="#bib0360"><span class="elsevierStyleSup">31</span></a> Os autores estudaram o polimorfismo CYP2J2 na psor&#237;ase&#44; uma doen&#231;a dermatol&#243;gica inflamat&#243;ria cr&#244;nica&#44; e observaram um risco aumentado de psor&#237;ase em pacientes com polimorfismo CYP2J2&#46; Na an&#225;lise agrupada&#44; que incluiu todos os pacientes com psor&#237;ase&#44; embora o polimorfismo do CYP tenha sido maior em pacientes com psor&#237;ase&#44; os resultados n&#227;o atingiram signific&#226;ncia estat&#237;stica&#46; Na an&#225;lise de subgrupos de subtipos de psor&#237;ase&#44; observou&#8208;se uma diferen&#231;a estatisticamente significativa entre o polimorfismo CYP em pacientes com PsV e o grupo controle&#46; O polimorfismo do CYP foi identificado como um fator de risco para PsV&#44; mas n&#227;o para PsnV&#46; A psor&#237;ase &#233; um dist&#250;rbio dermatol&#243;gico inflamat&#243;rio&#44; no qual a suscetibilidade gen&#233;tica tem um efeito significativo na patog&#234;nese da doen&#231;a&#46; O hist&#243;rico familiar de psor&#237;ase difere entre os grupos &#233;tnicos&#59; a preval&#234;ncia de hist&#243;rico familiar positivo &#233; estimada em aproximadamente 30&#37;&#46;<a class="elsevierStyleCrossRefs" href="#bib0365"><span class="elsevierStyleSup">32&#44;33</span></a> PSORS1 e PSORS2 s&#227;o dois dos <span class="elsevierStyleItalic">loci</span> de suscetibilidade mais conhecidos para a psor&#237;ase&#46; O HLA&#8208;C&#42;06&#58;02 est&#225; localizado no <span class="elsevierStyleItalic">locus</span> PSORS1 e o papel do HLA&#8208;C&#42;06&#58;02 na psor&#237;ase &#233; bem estabelecido&#46; Estudos recentes confirmaram a import&#226;ncia do HLA&#8208;C&#42;06&#58;02 na suscetibilidade gen&#233;tica da psor&#237;ase&#44; bem como seu impacto na resposta ao tratamento&#46;<a class="elsevierStyleCrossRef" href="#bib0375"><span class="elsevierStyleSup">34</span></a> Juntamente com o HLA&#8208;C&#42;06&#58;02&#44; um grande estudo gen&#233;tico feito por Zhou et al&#46; revelou v&#225;rios novos locais de suscetibilidade&#44; como HLA&#8208;C&#42;07&#58;04&#44; rs118179173&#44; HLA&#8208;B amino&#225;cido 67&#44; HLA&#8208;DPB1&#42;05&#58;01 e BTNL2 amino&#225;cido 281&#46;<a class="elsevierStyleCrossRef" href="#bib0380"><span class="elsevierStyleSup">35</span></a> O membro da fam&#237;lia de recrutamento de caspase 14 &#40;CARD14&#41; est&#225; localizado no <span class="elsevierStyleItalic">locus</span> PSORS2 e ativa a via NF&#8208;&#954;B&#46; O CARD14 foi classificado como um gene de suscetibilidade &#224; psor&#237;ase e muitos estudos recentes se propuseram a demonstrar o papel do CARD14 na patog&#234;nese da psor&#237;ase&#46; As muta&#231;&#245;es de ganho de fun&#231;&#227;o do CARD14 ativam a via de transdu&#231;&#227;o de sinal NF&#8208;&#954;B e foi demonstrado que a atividade aumentada do NF&#8208;&#954;B devido a muta&#231;&#245;es no CARD14 est&#225; ligada &#224; psor&#237;ase pustulosa&#46;<a class="elsevierStyleCrossRef" href="#bib0385"><span class="elsevierStyleSup">36</span></a> Zhu et al&#46; tamb&#233;m investigaram variantes do CARD14 em pacientes com PsV&#46; O estudo revelou cinco muta&#231;&#245;es&#44; mas as muta&#231;&#245;es tamb&#233;m foram observadas no grupo controle e n&#227;o foi poss&#237;vel estabelecer uma clara rela&#231;&#227;o muta&#231;&#227;o&#8208;doen&#231;a&#46;<a class="elsevierStyleCrossRef" href="#bib0390"><span class="elsevierStyleSup">37</span></a> Tanaka et al&#46; investigaram o papel imunol&#243;gico de CARD14 no modelo murino de psor&#237;ase e demonstraram que a express&#227;o do mRNA de IL&#8208;23 e a infiltra&#231;&#227;o de c&#233;lulas T produtoras de IL&#8208;17 diminu&#237;ram em camundongos com defici&#234;ncia de CARD14&#46;<a class="elsevierStyleCrossRef" href="#bib0395"><span class="elsevierStyleSup">38</span></a> O estudo tamb&#233;m mostrou que as altera&#231;&#245;es inflamat&#243;rias psoriasiformes da pele eram menores em camundongos com defici&#234;ncia de CARD14&#44; sugeriu o poss&#237;vel papel imunol&#243;gico inflamat&#243;rio da CARD14 na patog&#234;nese da psor&#237;ase&#46;<a class="elsevierStyleCrossRef" href="#bib0395"><span class="elsevierStyleSup">38</span></a> Al&#233;m do PSORS1 e PSORS2&#44; muitos <span class="elsevierStyleItalic">loci</span> de suscetibilidade &#224; psor&#237;ase foram identificados com estudos de associa&#231;&#227;o ampla do genoma &#40;<span class="elsevierStyleItalic">genome&#8208;wide association studies</span> &#91;GWAS&#93;&#41;&#46; Tsoi et al&#46; fizeram uma metan&#225;lise de GWAS e identificaram 16 novos locais de suscetibilidade que regulam I&#8208;&#954;B quinase&#47;via NF&#8208;&#954;B e citotoxicidade e que respondem a est&#237;mulos externos e diferencia&#231;&#227;o de leuc&#243;citos&#46;<a class="elsevierStyleCrossRef" href="#bib0400"><span class="elsevierStyleSup">39</span></a> Al&#233;m dessas varia&#231;&#245;es gen&#233;ticas&#44; tamb&#233;m foram identificadas algumas muta&#231;&#245;es e polimorfismos espec&#237;ficos do subtipo&#46; Li et al&#46; demonstraram que o polimorfismo no gene antagonista do receptor de IL&#8208;36 &#40;IL36RN&#41; estava associado ao aumento do risco de psor&#237;ase pustulosa&#46;<a class="elsevierStyleCrossRef" href="#bib0405"><span class="elsevierStyleSup">40</span></a> Twelves et al&#46; investigaram as frequ&#234;ncias de muta&#231;&#227;o IL36RN entre diferentes subtipos de psor&#237;ase pustulosa e observaram que as muta&#231;&#245;es IL36RN eram mais frequentes entre pacientes com psor&#237;ase pustulosa generalizada&#46;<a class="elsevierStyleCrossRef" href="#bib0410"><span class="elsevierStyleSup">41</span></a> Estudos com diferentes antecedentes gen&#233;ticos em diferentes subtipos de psor&#237;ase sugerem que a PsnV pode ser uma doen&#231;a diferente&#44; e n&#227;o um subtipo de psor&#237;ase&#44; o que &#233; consistente com os presentes resultados&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">No presente estudo&#44; n&#227;o foi observada associa&#231;&#227;o entre o polimorfismo CYP2J2 e as caracter&#237;sticas cl&#237;nicas da psor&#237;ase&#46; A maioria dos pacientes com psor&#237;ase inclu&#237;dos no estudo estava em tratamento&#46; Com o tratamento&#44; as principais caracter&#237;sticas cl&#237;nicas&#44; como PASI&#44; comprometimento das unhas&#44; artralgia e artrite podem ser modificadas&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">Uma das limita&#231;&#245;es deste estudo &#233; que ele n&#227;o verificou as concentra&#231;&#245;es de EET e sua associa&#231;&#227;o com o polimorfismo do CYP2J2&#46; O polimorfismo do CYP2J2 pode contribuir para o processo inflamat&#243;rio e a patog&#234;nese da psor&#237;ase pela altera&#231;&#227;o das concentra&#231;&#245;es de ETT&#59; por&#233;m&#44; mais estudos s&#227;o necess&#225;rios para compreender a rela&#231;&#227;o entre psor&#237;ase e polimorfismo do CYP&#8208;ETT&#46; Outra limita&#231;&#227;o foi o n&#250;mero restrito de pacientes com psor&#237;ase com comorbidades cardiovasculares&#46; O presente estudo n&#227;o demonstrou rela&#231;&#227;o entre o polimorfismo do CYP e as comorbidades&#44; mas isso pode ser devido ao erro do tipo II &#40;beta&#41;&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">A base gen&#233;tica da psor&#237;ase &#233; complexa e difere entre os grupos &#233;tnicos e os subtipos de psor&#237;ase&#46; O polimorfismo CPY &#8211; como outros polimorfismos &#8211; pode variar entre os grupos &#233;tnicos&#46; Para generalizar os presentes resultados&#44; s&#227;o necess&#225;rios estudos adicionais com diferentes grupos &#233;tnicos e diferentes subtipos de psor&#237;ase&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Suporte financeiro</span><p id="par0105" class="elsevierStylePara elsevierViewall">Bolsa de pesquisa da Sociedade Turca de Dermatologia &#40;2017&#47;53&#41;&#46;</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Contribui&#231;&#227;o dos autores</span><p id="par0110" class="elsevierStylePara elsevierViewall">Y&#305;ld&#305;z Hayran&#58; An&#225;lise estat&#237;stica&#59; aprova&#231;&#227;o da vers&#227;o final do manuscrito&#59; concep&#231;&#227;o e planejamento do estudo&#59; elabora&#231;&#227;o e reda&#231;&#227;o do manuscrito&#59; obten&#231;&#227;o&#44; an&#225;lise e interpreta&#231;&#227;o dos dados&#59; participa&#231;&#227;o efetiva na orienta&#231;&#227;o da pesquisa&#59; participa&#231;&#227;o intelectual em conduta proped&#234;utica e&#47;ou terap&#234;utica de casos estudados&#59; revis&#227;o cr&#237;tica da literatura&#59; revis&#227;o cr&#237;tica do manuscrito&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">Nuran All&#305;&#58; Aprova&#231;&#227;o da vers&#227;o final do manuscrito&#59; revis&#227;o cr&#237;tica do manuscrito&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">P&#305;nar &#304;ncel Uysal&#58; Elabora&#231;&#227;o e reda&#231;&#227;o do manuscrito&#59; obten&#231;&#227;o&#44; an&#225;lise e interpreta&#231;&#227;o dos dados&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">Tuba &#199;andar&#58; Participa&#231;&#227;o efetiva na orienta&#231;&#227;o da pesquisa&#59; revis&#227;o cr&#237;tica do manuscrito&#46;</p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Conflitos de interesse</span><p id="par0130" 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">O citocromo P450 &#40;CYP&#41; 2J2 &#233; principalmente expresso em tecidos extra&#8208;hep&#225;ticos&#46; Ele metaboliza o &#225;cido araquid&#244;nico &#40;AA&#41; em &#225;cidos epoxieicosatrienoicos &#40;EETs&#41;&#44; com v&#225;rios efeitos cardioprotetores e anti&#8208;inflamat&#243;rios&#46; O polimorfismo do CYP2J2 foi identificado como um fator de risco para doen&#231;as cardiovasculares&#44; mas sua associa&#231;&#227;o com a psor&#237;ase permanece desconhecida&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Objetivo</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Avaliar se o polimorfismo do CYP2J2 &#233; um fator de risco para psor&#237;ase em uma popula&#231;&#227;o turca&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">M&#233;todos</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">O estudo incluiu 94 pacientes com psor&#237;ase e 100 controles saud&#225;veis&#44; pareados por idade e sexo&#46; Caracter&#237;sticas demogr&#225;ficas e cl&#237;nicas detalhadas foram registradas e os escores do &#205;ndice de &#193;rea e Gravidade da Psor&#237;ase &#40;PASI&#44; do ingl&#234;s <span class="elsevierStyleItalic">Psoriasis Area and Severity Index</span>&#41; foram calculados para pacientes com psor&#237;ase&#46; Amostras de sangue venoso foram coletadas de todos os participantes e o polimorfismo CYP2J2 50G<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>T &#40;rs890293&#41; foi analisado por rea&#231;&#227;o em cadeia da polimerase &#40;PCR&#41;&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Resultados</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">As frequ&#234;ncias do alelo T e do gen&#243;tipo TT<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>GT aumentaram em pacientes com psor&#237;ase vulgar &#40;PsV&#41; em compara&#231;&#227;o ao grupo controle &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;024 e p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;029&#44; respectivamente&#59; OR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>2&#44;82&#59; IC 95&#37;&#58;&#160;1&#44;11&#8211;7&#44;15&#41;&#46; N&#227;o foi identificada associa&#231;&#227;o entre o polimorfismo do CYP2J2 e as caracter&#237;sticas cl&#237;nicas da psor&#237;ase&#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">Um n&#250;mero reduzido de pacientes foi inclu&#237;do no estudo&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Conclus&#227;o</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">O polimorfismo CYP2J2 50G<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>T &#40;rs890293&#41; foi associado a um risco aumentado de PsV na popula&#231;&#227;o turca&#46;</p></span>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0015">Como citar este artigo&#58; Hayran Y&#44; All&#305; N&#44; Uysal P&#304;&#44; &#199;andar T&#46; Association of CYP2J2 polymorphism with susceptibility to psoriasis in Turkish population&#58; a case&#8208;control study&#46; An Bras Dermatol&#46; 2020&#59;95&#58;25&#8211;31&#46;</p>"
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          "pt" => "<p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Caracter&#237;sticas dos pacientes e caracter&#237;sticas cl&#237;nicas da psor&#237;ase</p>"
        ]
      ]
      2 => array:8 [
        "identificador" => "tbl0015"
        "etiqueta" => "Tabela 3"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at3"
            "detalle" => "Tabela "
            "rol" => "short"
          ]
        ]
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">PsV&#44; psor&#237;ase vulgar&#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="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&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">Psor&#237;ase &#40;todas as formas&#59; n &#61; 94&#41;n &#40;&#37;&#41;&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">PsV &#40;n &#61; 71&#41;n &#40;&#37;&#41;&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">Controle &#40;n &#61; 100&#41;n &#40;&#37;&#41;&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">p&#40;psor&#237;ase &#91;todas as formas&#93; <span class="elsevierStyleItalic">vs</span>&#46; controle&#41;&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">p&#40;PsV <span class="elsevierStyleItalic">vs</span>&#46; controle&#41;&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">OR &#40;IC 95&#37;&#41;&#40;psor&#237;ase &#91;todas as formas&#93; <span class="elsevierStyleItalic">vs</span>&#46; controle&#41;&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">OR &#40;IC 95&#37;&#41;&#40;PsV <span class="elsevierStyleItalic">vs</span>&#46; controle&#41;&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="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&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" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">Gen&#243;tipo</span></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="" 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" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Modelo dominante</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">TT&#43;GT&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">16 &#40;17&#44;02&#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;19&#44;8&#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">8 &#40;8&#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">0&#44;062&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&#44;029&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">2&#44;35 &#40;0&#44;96&#63;5&#44;8&#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">2&#44;82 &#40;1&#44;11&#63;7&#44;15&#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">GG&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">78 &#40;82&#44;97&#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">57 &#40;80&#44;2&#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">92 &#40;92&#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><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></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="9" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Modelo recessivo</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">TT&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">1 &#40;1&#44;06&#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">1 &#40;1&#44;4&#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">1 &#40;1&#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">0&#44;96&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&#44;807&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">1&#44;07 &#40;0&#44;07&#63;17&#44;3&#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">1&#44;41 &#40;0&#44;09&#63;22&#44;9&#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">GT&#43;GG&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">93 &#40;98&#44;94&#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">70 &#40;98&#44;6&#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">99 &#40;99&#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><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></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">Alelo</span></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="" 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" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\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">G&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">171 &#40;90&#44;96&#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">127 &#40;89&#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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">191 &#40;91&#44;2&#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">0&#44;063&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&#44;024&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
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Investigação
Associação entre polimorfismo CYP2J2 e suscetibilidade à psoríase na população turca: estudo caso‐controle
Yıldız Hayrana,
Corresponding author
yildiz_kantarci@yahoo.com

Autor para correspondência.
, Nuran Allıa, Pınar İncel Uysala, Tuba Çandarb
a Departamento de Dermatologia, Ankara Numune Training and Research Hospital, Ankara, Turquia
b Departamento de Bioquímica Médica, Ufuk University Faculty of Medicine, Ankara, Turquia
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Introdu&#231;&#227;o</span><p id="par0005" class="elsevierStylePara elsevierViewall">A psor&#237;ase &#233; uma doen&#231;a dermatol&#243;gica inflamat&#243;ria cr&#244;nica&#44; caracterizada por p&#225;pulas e placas bem delimitadas com escamas prateadas&#46; No entanto&#44; os estudos relatam uma ampla varia&#231;&#227;o na preval&#234;ncia &#40;0&#8211;11&#44;8&#37;&#41;&#44; de acordo com idade&#44; sexo e etnia&#46; Acredita&#8208;se que a psor&#237;ase afete cerca de 2&#37; da popula&#231;&#227;o em geral&#44;<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">1</span></a> incide igualmente em homens e mulheres&#46; Embora possa come&#231;ar em qualquer idade&#44; foram observados dois picos et&#225;rios de incid&#234;ncia&#58; o primeiro na segunda e terceira d&#233;cadas e o segundo na quinta e sexta d&#233;cadas&#46;<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">2</span></a> O comprometimento de pele&#44; unhas ou articula&#231;&#245;es pode ser observado em at&#233; 50&#37; dos pacientes&#46; A associa&#231;&#227;o da psor&#237;ase com v&#225;rios dist&#250;rbios sist&#234;micos&#44; como doen&#231;as cardiovasculares&#44; infec&#231;&#245;es&#44; dist&#250;rbios metab&#243;licos&#44; doen&#231;as renais&#44; doen&#231;as gastrintestinais e c&#226;ncer&#44; est&#225; bem documentada&#46;<a class="elsevierStyleCrossRefs" href="#bib0220"><span class="elsevierStyleSup">3&#8211;5</span></a> A etiopatog&#234;nese da doen&#231;a ainda n&#227;o est&#225; bem esclarecida&#46; A psor&#237;ase &#233; classificada como uma doen&#231;a multifatorial&#59; fatores gen&#233;ticos&#44; ambientais&#44; imunol&#243;gicos e inflamat&#243;rios contribuem para sua patog&#234;nese&#46;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">6</span></a> Inflama&#231;&#227;o&#44; tanto lesional quanto sist&#234;mica&#44; &#233; uma caracter&#237;stica importante da psor&#237;ase&#46; Muitos estudos que avaliaram a inflama&#231;&#227;o sist&#234;mica na psor&#237;ase apontaram que marcadores de inflama&#231;&#227;o &#40;especialmente prote&#237;na C&#8208;reativa&#44; fator de necrose tumoral &#91;TNF&#93;&#8208;&#945;&#44; mol&#233;cula de ades&#227;o intercelular &#91;ICAM&#93;&#8208;1&#44; E&#8208;selectina e interleucinas &#91;IL&#93;&#8208;1&#946;&#44; IL &#8208;6&#44; IL&#8208;10&#41; est&#227;o aumentados em pacientes psori&#225;sicos&#44; criam um estado inflamat&#243;rio sist&#234;mico que pode levar a comorbidades como doen&#231;as cardiovasculares&#46;<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">7</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">As enzimas do citocromo P450 &#40;CYP&#41; s&#227;o hemoprote&#237;nas localizadas principalmente no ret&#237;culo endoplasm&#225;tico &#40;RE&#41; ou na membrana mitocondrial em humanos&#46; A principal fun&#231;&#227;o dos CYPs &#233; metabolizar medicamentos&#44; xenobi&#243;ticos n&#227;o medicamentosos e endobi&#243;ticos&#44; como &#225;cidos graxos&#44; esteroides e horm&#244;nios esteroides&#44; &#225;cidos biliares&#44; vitamina D&#44; prostaglandinas e &#225;cido araquid&#244;nico &#40;AA&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0245"><span class="elsevierStyleSup">8&#8211;10</span></a> O AA &#233; metabolizado em quatro &#225;cidos epoxieicosatrienoicos &#40;EETs&#41; 5&#44;6&#8208;EET&#44; 8&#44;9&#8208;EET&#44; 11&#44;12&#8208;EET e 14&#44;15&#8208;EET&#46; Os EETs promovem relaxamento vascular&#44; t&#234;m efeito anti&#8208;inflamat&#243;rio no endot&#233;lio e efeito cardioprotetor durante eventos isqu&#234;micos&#46;<a class="elsevierStyleCrossRefs" href="#bib0260"><span class="elsevierStyleSup">11&#44;12</span></a> Al&#233;m de seu efeito favor&#225;vel sobre doen&#231;as cardiovasculares e inflamat&#243;rias&#44; os EETs tamb&#233;m podem promover prolifera&#231;&#227;o&#44; migra&#231;&#227;o e sobreviv&#234;ncia nas c&#233;lulas tumorais&#46;<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">13</span></a> O CYP2J2 &#40;isoforma do CYP&#44; expresso principalmente no f&#237;gado&#44; cora&#231;&#227;o&#44; intestino delgado&#44; rim e c&#233;rebro&#41; &#233; um dos principais CYPs que convertem AA em EETs&#46;<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">14</span></a> O polimorfismo do CYP2J2 foi estudado em doen&#231;as cardiovasculares&#44; acidente vascular cerebral isqu&#234;mico e doen&#231;a de Alzheimer e demonstrou&#8208;se que ele aumenta a suscetibilidade a essas doen&#231;as&#46;<a class="elsevierStyleCrossRefs" href="#bib0280"><span class="elsevierStyleSup">15&#8211;18</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">O objetivo deste estudo foi investigar o polimorfismo do CYP2J2 na psor&#237;ase&#44; uma doen&#231;a dermatol&#243;gica inflamat&#243;ria cr&#244;nica que pode ser acompanhada por doen&#231;as cardiovasculares&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Material e m&#233;todos</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Popula&#231;&#227;o do estudo</span><p id="par0020" class="elsevierStylePara elsevierViewall">No presente estudo&#44; 94 pacientes com psor&#237;ase diagnosticada cl&#237;nica ou histopatologicamente foram admitidos no Hospital de Pesquisa e Treinamento Ankara Numune entre janeiro de 2015 e julho de 2016&#46; Como grupo controle&#44; foram recrutados 100 pacientes pareados por sexo e idade admitidos no ambulat&#243;rio de dermatologia&#44; com uma doen&#231;a dermatol&#243;gica que n&#227;o psor&#237;ase e sem hist&#243;rico de doen&#231;a inflamat&#243;ria cr&#244;nica&#46; As caracter&#237;sticas demogr&#225;ficas e cl&#237;nicas &#40;subtipo da doen&#231;a&#44; dura&#231;&#227;o&#44; gravidade&#44; hist&#243;rico familiar&#44; tratamentos&#44; hist&#243;rico de artrite psori&#225;sica e comprometimento de localiza&#231;&#227;o especial&#44; como couro cabeludo&#44; &#225;reas flexurais e unhas&#41; dos pacientes com psor&#237;ase e do grupo controle foram registradas&#46; A artrite psori&#225;sica foi avaliada em todos os pacientes&#46; O hist&#243;rico de artrite psori&#225;sica foi coletado&#59; os pacientes com artralgia ou artrite ativa foram encaminhados ao departamento de reumatologia para um diagn&#243;stico definitivo de artrite psori&#225;sica&#46; Pacientes com idade<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>18&#44; participantes gr&#225;vidas ou lactantes e participantes com hist&#243;rico de doen&#231;as imunol&#243;gicas ou inflamat&#243;rias foram exclu&#237;dos do estudo&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">O estudo foi aprovado pelo comit&#234; de &#233;tica local &#40;E&#8208;15&#8208;612&#41; e todos os participantes assinaram um termo de consentimento livre e esclarecido antes do estudo&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">An&#225;lise do polimorfismo</span><p id="par0030" class="elsevierStylePara elsevierViewall">O desenho do <span class="elsevierStyleItalic">primer</span> foi feito para a amplifica&#231;&#227;o por rea&#231;&#227;o em cadeia da polimerase &#40;PCR&#41; da regi&#227;o do polimorfismo CYP2J2 &#8208;50G<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>T&#44; de modo que o local do polimorfismo estivesse a 150<span class="elsevierStyleHsp" style=""></span>bp de ambas as extremidades do <span class="elsevierStyleItalic">amplicon</span> de PCR&#46; Isso foi necess&#225;rio porque foi usado um kit de sequenciamento que faz a leitura a 150 pb das duas extremidades&#46; Antes de pedirem os <span class="elsevierStyleItalic">primers</span>&#44; os autores adicionaram sequ&#234;ncias espec&#237;ficas de cerca de 30 nucleot&#237;dios &#224;s extremidades 5&#8217; dos <span class="elsevierStyleItalic">primers</span>&#44; para tornar os <span class="elsevierStyleItalic">amplicons</span> adequados para o sequenciamento indexado nas plataformas Illumina&#46; A <a class="elsevierStyleCrossRef" href="#tbl0005">tabela 1</a> resume os pares de <span class="elsevierStyleItalic">primers</span> de PCR&#44; as sequ&#234;ncias espec&#237;ficas de <span class="elsevierStyleItalic">locus</span> e as sequ&#234;ncias adicionadas para a PCR &#237;ndice&#46; As amostras de DNA foram obtidas isolando&#8208;se 200<span class="elsevierStyleHsp" style=""></span>&#956;L de amostras de sangue de cada participante&#44; com um QIAamp DNA Blood Mini Kit &#40;Qiagen Inc&#46;&#41;&#46; As PCRs foram feitas em amostras de DNA isoladas com os <span class="elsevierStyleItalic">primers</span> projetados&#59; as rea&#231;&#245;es foram verificadas usando eletroforese em gel de agarose a 2&#37;&#46; Uma segunda PCR para fins de indexa&#231;&#227;o foi feita para adicionar sequ&#234;ncias &#237;ndice aos <span class="elsevierStyleItalic">amplicons</span>&#44; para alcan&#231;ar a multiplexa&#231;&#227;o no sequenciamento de pr&#243;ximo gene&#46; Para cada uma das amostras&#44; foi usada uma combina&#231;&#227;o diferente de <span class="elsevierStyleItalic">primers</span> &#237;ndice&#46; As rea&#231;&#245;es de indexa&#231;&#227;o por PCR tamb&#233;m foram verificadas com eletroforese em gel de agarose a 2&#37;&#46; Volumes iguais de rea&#231;&#245;es de PCR indexadas foram misturados para obter um <span class="elsevierStyleItalic">pool</span> de PCR&#44; que inclu&#237;a todos os <span class="elsevierStyleItalic">amplicons</span> de todas as amostras&#46; O <span class="elsevierStyleItalic">pool</span> de PCR foi purificado com um kit NucleoFast&#174; 96&#160;PCR &#40;Macherey&#8208;Nagel GmbH&#41;&#46; O <span class="elsevierStyleItalic">pool</span> purificado foi quantificado com um espectrofot&#244;metro de microvolume e dilu&#237;do de acordo com as recomenda&#231;&#245;es da Illumina Inc&#46; O sequenciamento de segunda gera&#231;&#227;o das amostras foi feito com o sistema Miseq &#40;Illumina Inc&#46;&#41;&#46; A genotipagem das amostras foi finalizada quando os dados foram analisados no <span class="elsevierStyleItalic">software</span> IGV&#160;v&#46; 2&#46;3 &#40;Broad Institute&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">An&#225;lise estat&#237;stica</span><p id="par0035" class="elsevierStylePara elsevierViewall">O SPSS Statistics para Windows v&#46; 21&#46;0 &#40;IBM Corp&#46; &#8211; Armonk&#44; NY&#44; Estados Unidos&#41; foi usado para an&#225;lise estat&#237;stica&#46; As vari&#225;veis quantitativas foram analisadas com o teste qui&#8208;quadrado ou o teste exato de Fisher&#44; quando necess&#225;rio&#59; as vari&#225;veis qualitativas foram analisadas com o teste U de Mann&#8208;Whitney&#46; A correla&#231;&#227;o entre vari&#225;veis qualitativas foi avaliada pelo teste de correla&#231;&#227;o de Spearman&#46; Valores&#8208;p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;05 foram considerados como diferen&#231;as estatisticamente significativas em todas as an&#225;lises&#46;</p></span></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Resultados</span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Caracter&#237;sticas dos pacientes e caracter&#237;sticas cl&#237;nicas da psor&#237;ase</span><p id="par0040" class="elsevierStylePara elsevierViewall">As caracter&#237;sticas dos pacientes e os aspectos cl&#237;nicos da psor&#237;ase est&#227;o resumidos na <a class="elsevierStyleCrossRef" href="#tbl0005">tabela 1</a>&#46; Na distribui&#231;&#227;o por sexo&#44; 47&#37; dos pacientes eram do sexo masculino e 53&#37; do feminino&#46; A idade m&#233;dia dos pacientes foi de 44&#44;66 anos &#40;DP<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>12&#44;6&#41; e a idade m&#233;dia ao diagn&#243;stico de psor&#237;ase foi de 33&#44;21 anos &#40;DP<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>14&#44;9&#41;&#46; A idade dos pacientes e a idade ao diagn&#243;stico foram semelhantes nos pacientes do sexo masculino e feminino &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;39 e 0&#44;53&#44; respectivamente&#41;&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">O PASI m&#233;dio dos pacientes com psor&#237;ase foi 4&#44;51 &#40;DP<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>3&#44;86&#41;&#46; A psor&#237;ase vulgar &#40;PsV&#41; foi o tipo mais comum&#44; identificada em 76&#37; de todos os pacientes com psor&#237;ase&#46; A psor&#237;ase palmoplantar foi o segundo tipo mais comum &#40;11&#37;&#41;&#44; seguida pela gutata &#40;6&#37;&#41;&#44; eritrod&#233;rmica &#40;4&#37;&#41; e pustulosa &#40;3&#37;&#41;&#46; O comprometimento de pelo menos uma das localiza&#231;&#245;es especiais&#44; como couro cabeludo&#44; regi&#227;o flexural ou regi&#227;o genital&#44; foi observado em 74&#44;5&#37; dos pacientes com psor&#237;ase&#46; O couro cabeludo foi a localiza&#231;&#227;o especial mais frequentemente afetada&#46; Artralgia foi identificada em 47&#37; dos pacientes com psor&#237;ase e 23&#37; dos pacientes foram diagnosticados com artrite psori&#225;sica&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">Os tratamentos anteriores e atuais est&#227;o resumidos na <a class="elsevierStyleCrossRef" href="#tbl0010">tabela 2</a>&#46; Os esteroides t&#243;picos foram o tratamento anterior e atual mais comum em pacientes com psor&#237;ase &#40;99&#37; e 90&#37;&#44; respectivamente&#41;&#46; Entre os pacientes&#44; 23&#44;1&#37; apresentavam pelo menos uma doen&#231;a sist&#234;mica ou comorbidade associada&#46; Doen&#231;as cardiovasculares foram observadas em 11&#44;7&#37; dos pacientes&#44; e outras doen&#231;as sist&#234;micas em 22&#44;2&#37; &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">tabela 2</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">An&#225;lise do polimorfismo do gene CYP2J2</span><p id="par0055" class="elsevierStylePara elsevierViewall">A frequ&#234;ncia al&#233;lica e a distribui&#231;&#227;o do gen&#243;tipo do gene CYP2J2 em pacientes com psor&#237;ase e controles est&#227;o descritas na <a class="elsevierStyleCrossRef" href="#tbl0015">tabela 3</a>&#46; O alelo T e o gen&#243;tipo TT<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>GT no modelo dominante foram mais frequentes em pacientes com psor&#237;ase em compara&#231;&#227;o com os controles &#40;frequ&#234;ncia do alelo T 9&#44;04&#37; <span class="elsevierStyleItalic">vs</span>&#46; 4&#44;5&#37; e frequ&#234;ncia do gen&#243;tipo TT<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>GT 17&#44;02&#37; <span class="elsevierStyleItalic">vs</span>&#46; 8&#37;&#41;&#44; mas essa diferen&#231;a cl&#237;nica n&#227;o foi estatisticamente significativa &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;063 e p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;062&#44; respectivamente&#41;&#46; Os pacientes com psor&#237;ase foram divididos em dois subgrupos&#58; vulgar &#40;PsV&#41; e n&#227;o vulgar &#40;nVP&#41;&#46; A an&#225;lise de subgrupos mostrou que as frequ&#234;ncias do alelo T e do gen&#243;tipo TT<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>GT eram maiores em pacientes com PsV em compara&#231;&#227;o com o grupo controle &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;024 e p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;029&#44; respectivamente&#41;&#44; indicou que o polimorfismo do CYP2J2 estava associado a um aumento do risco de desenvolver PsV &#40;OR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>2&#44;82&#59; IC 95&#37;&#58;&#160;1&#44;11&#8208;7&#44;15&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;029&#41;&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0060" class="elsevierStylePara elsevierViewall">As caracter&#237;sticas demogr&#225;ficas e as caracter&#237;sticas da doen&#231;a de pacientes com psor&#237;ase com gen&#243;tipo GG &#40;tipo selvagem&#41; e gen&#243;tipo GT<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>TT &#40;polimorfismo homozigoto ou heterozigoto&#41; foram comparadas e resumidas na <a class="elsevierStyleCrossRef" href="#tbl0020">tabela 4</a>&#46; Embora o grupo polim&#243;rfico apresentasse mais pacientes com PsV do que pacientes com PsnV &#40;&#62; 2 vezes&#41;&#44; o resultado n&#227;o foi estatisticamente significativo &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;22&#41;&#46; A idade e o sexo dos pacientes&#44; idade ao in&#237;cio da doen&#231;a&#44; PASI&#44; presen&#231;a de comprometimento de localiza&#231;&#245;es especiais&#44; presen&#231;a de artralgia e artrite&#44; hist&#243;rico familiar positivo para psor&#237;ase&#44; presen&#231;a de doen&#231;as associadas e modalidades de tratamento foram semelhantes entre pacientes com psor&#237;ase com e sem polimorfismo&#46;</p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia></span></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Discuss&#227;o</span><p id="par0065" class="elsevierStylePara elsevierViewall">Este estudo investigou o poss&#237;vel papel do polimorfismo do CYP2J2 como fator de risco em pacientes com psor&#237;ase&#46; Os resultados demonstram uma frequ&#234;ncia significativamente mais alta do alelo T em pacientes com PsV e um risco aumentado de psor&#237;ase em pacientes com polimorfismo CYP2J2 no modelo dominante&#46; Tanto quanto &#233; do conhecimento dos autores&#44; este &#233; o primeiro estudo que investiga o papel do polimorfismo CYP2J2 na psor&#237;ase&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">O CYP2J2 50G<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>T &#233; um dos polimorfismos funcionais do CYP2J2 mais estudados&#46; Spiecker et al&#46; estudaram o efeito do polimorfismo CYP2J2 50G<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>T e observaram uma diminui&#231;&#227;o na liga&#231;&#227;o do fator de transcri&#231;&#227;o Sp1 ao DNA&#44; uma redu&#231;&#227;o na atividade do promotor e menores concentra&#231;&#245;es plasm&#225;ticas de EET em pacientes com polimorfismo G&#8208;50T em compara&#231;&#227;o com participantes com tipo selvagem&#46;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">19</span></a> EETs derivados do CYP2J2 induzem vasodilata&#231;&#227;o&#44; inibem inflama&#231;&#227;o&#44; apoptose e trombose e apresentam efeitos cardioprotetores&#46;<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">20</span></a> Ao alterar suas concentra&#231;&#245;es plasm&#225;ticas&#44; o polimorfismo do CYP pode afetar o papel cardioprotetor dos EETs e desempenhar um papel na patog&#234;nese das doen&#231;as cardiovasculares&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">O polimorfismo do CYP2J2 foi estudado principalmente em doen&#231;as cardiovasculares&#44; apresentou resultados contradit&#243;rios entre diferentes grupos &#233;tnicos&#46; Estudos que investigaram o polimorfismo CYP2J2 em doen&#231;as coronarianas revelaram um aumento do risco na popula&#231;&#227;o alem&#227;&#44; diminui&#231;&#227;o do risco em negros e nenhuma associa&#231;&#227;o em brancos e na popula&#231;&#227;o sueca&#46;<a class="elsevierStyleCrossRefs" href="#bib0295"><span class="elsevierStyleSup">18&#44;19&#44;21&#44;22</span></a> Polonikov et al&#46; evidenciaram um risco aumentado de hipertens&#227;o em pacientes russos&#59; no entanto&#44; essa associa&#231;&#227;o n&#227;o foi confirmada em negros ou brancos&#46;<a class="elsevierStyleCrossRefs" href="#bib0320"><span class="elsevierStyleSup">23&#8211;25</span></a> Polonikov et al&#46; tamb&#233;m descreveram uma rela&#231;&#227;o sexo&#8208;espec&#237;fica entre o polimorfismo do CYP2J2 e a hipertens&#227;o em pacientes russas do sexo feminino&#46;<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">26</span></a> N&#227;o foi identificada associa&#231;&#227;o significativa entre o polimorfismo CYP2J2 e acidente vascular cerebral nas popula&#231;&#245;es sueca e chinesa&#46;<a class="elsevierStyleCrossRefs" href="#bib0295"><span class="elsevierStyleSup">18&#44;27</span></a> Estudos recentes tamb&#233;m demonstraram que o CYP2J2 aumentou os n&#237;veis circulantes de EET e angiog&#234;nese induzida e melhorou a fun&#231;&#227;o card&#237;aca em ratos ap&#243;s infarto do mioc&#225;rdio&#46;<a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">28</span></a> As doen&#231;as cardiovasculares s&#227;o comorbidades frequentes e importantes na psor&#237;ase&#46; O presente estudo avaliou a associa&#231;&#227;o entre polimorfismo do CYP2J2 e comorbidades cardiovasculares&#46; N&#227;o foi observada uma associa&#231;&#227;o significativa entre o polimorfismo do CYP2J2 e a frequ&#234;ncia de comorbidade&#44; sugeriu&#8208;se que o CYP2J2 pode aumentar o risco do surgimento de PsV&#44; mas n&#227;o est&#225; associado a um risco aumentado de comorbidades cardiovasculares em pacientes com psor&#237;ase&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">Al&#233;m de seus efeitos cardiovasculares&#44; os EETs derivados do CYP2J2 tamb&#233;m modulam a inflama&#231;&#227;o&#46;<a class="elsevierStyleCrossRef" href="#bib0350"><span class="elsevierStyleSup">29</span></a> Node et al&#46; estudaram o efeito dos EETs derivados do CYP2J2 na inflama&#231;&#227;o vascular&#46; Seu estudo revelou que os EETs podem modular a resposta inflamat&#243;ria pela inibi&#231;&#227;o da express&#227;o induzida por citocinas pr&#243;&#8208;inflamat&#243;rias &#40;TNF&#8208;&#945;&#44; IL&#8208;1&#945; e lipopolissacar&#237;dio bacteriano&#41; das mol&#233;culas de ades&#227;o endotelial vascular &#40;VCAM&#8208;1&#44; ICAM&#8208;1 e E&#8208;selectin&#41; e diminuir o n&#250;mero de leuc&#243;citos mononucleares m&#243;veis&#47;aderentes&#46;<a class="elsevierStyleCrossRef" href="#bib0350"><span class="elsevierStyleSup">29</span></a> Os EETs tamb&#233;m apresentam efeitos anti&#8208;inflamat&#243;rios pela inibi&#231;&#227;o do fator nuclear kappaB &#40;NF&#8208;&#954;B&#41; e I&#954;B quinase&#44; ativa&#231;&#227;o dos receptores ativados pelo proliferador de peroxissoma&#44; aumento da express&#227;o da eNOS e regula&#231;&#227;o da homeostase do ret&#237;culo endoplasm&#225;tico&#46;<a class="elsevierStyleCrossRef" href="#bib0355"><span class="elsevierStyleSup">30</span></a></p><p id="par0085" class="elsevierStylePara elsevierViewall">Embora o efeito anti&#8208;inflamat&#243;rio dos EETs esteja bem documentado&#44; poucos estudos investigaram o polimorfismo do CYP2J2 em doen&#231;as inflamat&#243;rias&#46; Wang et al&#46; estudaram o polimorfismo do CYP2J2 em pacientes com diabetes <span class="elsevierStyleItalic">mellitus</span>&#46; Embora n&#227;o tenha sido observada diferen&#231;a significativa entre pacientes diab&#233;ticos e um grupo controle&#44; em pacientes diab&#233;ticos o polimorfismo do CYP2J2 demonstrou estar associado a menor idade de in&#237;cio&#46;<a class="elsevierStyleCrossRef" href="#bib0360"><span class="elsevierStyleSup">31</span></a> Os autores estudaram o polimorfismo CYP2J2 na psor&#237;ase&#44; uma doen&#231;a dermatol&#243;gica inflamat&#243;ria cr&#244;nica&#44; e observaram um risco aumentado de psor&#237;ase em pacientes com polimorfismo CYP2J2&#46; Na an&#225;lise agrupada&#44; que incluiu todos os pacientes com psor&#237;ase&#44; embora o polimorfismo do CYP tenha sido maior em pacientes com psor&#237;ase&#44; os resultados n&#227;o atingiram signific&#226;ncia estat&#237;stica&#46; Na an&#225;lise de subgrupos de subtipos de psor&#237;ase&#44; observou&#8208;se uma diferen&#231;a estatisticamente significativa entre o polimorfismo CYP em pacientes com PsV e o grupo controle&#46; O polimorfismo do CYP foi identificado como um fator de risco para PsV&#44; mas n&#227;o para PsnV&#46; A psor&#237;ase &#233; um dist&#250;rbio dermatol&#243;gico inflamat&#243;rio&#44; no qual a suscetibilidade gen&#233;tica tem um efeito significativo na patog&#234;nese da doen&#231;a&#46; O hist&#243;rico familiar de psor&#237;ase difere entre os grupos &#233;tnicos&#59; a preval&#234;ncia de hist&#243;rico familiar positivo &#233; estimada em aproximadamente 30&#37;&#46;<a class="elsevierStyleCrossRefs" href="#bib0365"><span class="elsevierStyleSup">32&#44;33</span></a> PSORS1 e PSORS2 s&#227;o dois dos <span class="elsevierStyleItalic">loci</span> de suscetibilidade mais conhecidos para a psor&#237;ase&#46; O HLA&#8208;C&#42;06&#58;02 est&#225; localizado no <span class="elsevierStyleItalic">locus</span> PSORS1 e o papel do HLA&#8208;C&#42;06&#58;02 na psor&#237;ase &#233; bem estabelecido&#46; Estudos recentes confirmaram a import&#226;ncia do HLA&#8208;C&#42;06&#58;02 na suscetibilidade gen&#233;tica da psor&#237;ase&#44; bem como seu impacto na resposta ao tratamento&#46;<a class="elsevierStyleCrossRef" href="#bib0375"><span class="elsevierStyleSup">34</span></a> Juntamente com o HLA&#8208;C&#42;06&#58;02&#44; um grande estudo gen&#233;tico feito por Zhou et al&#46; revelou v&#225;rios novos locais de suscetibilidade&#44; como HLA&#8208;C&#42;07&#58;04&#44; rs118179173&#44; HLA&#8208;B amino&#225;cido 67&#44; HLA&#8208;DPB1&#42;05&#58;01 e BTNL2 amino&#225;cido 281&#46;<a class="elsevierStyleCrossRef" href="#bib0380"><span class="elsevierStyleSup">35</span></a> O membro da fam&#237;lia de recrutamento de caspase 14 &#40;CARD14&#41; est&#225; localizado no <span class="elsevierStyleItalic">locus</span> PSORS2 e ativa a via NF&#8208;&#954;B&#46; O CARD14 foi classificado como um gene de suscetibilidade &#224; psor&#237;ase e muitos estudos recentes se propuseram a demonstrar o papel do CARD14 na patog&#234;nese da psor&#237;ase&#46; As muta&#231;&#245;es de ganho de fun&#231;&#227;o do CARD14 ativam a via de transdu&#231;&#227;o de sinal NF&#8208;&#954;B e foi demonstrado que a atividade aumentada do NF&#8208;&#954;B devido a muta&#231;&#245;es no CARD14 est&#225; ligada &#224; psor&#237;ase pustulosa&#46;<a class="elsevierStyleCrossRef" href="#bib0385"><span class="elsevierStyleSup">36</span></a> Zhu et al&#46; tamb&#233;m investigaram variantes do CARD14 em pacientes com PsV&#46; O estudo revelou cinco muta&#231;&#245;es&#44; mas as muta&#231;&#245;es tamb&#233;m foram observadas no grupo controle e n&#227;o foi poss&#237;vel estabelecer uma clara rela&#231;&#227;o muta&#231;&#227;o&#8208;doen&#231;a&#46;<a class="elsevierStyleCrossRef" href="#bib0390"><span class="elsevierStyleSup">37</span></a> Tanaka et al&#46; investigaram o papel imunol&#243;gico de CARD14 no modelo murino de psor&#237;ase e demonstraram que a express&#227;o do mRNA de IL&#8208;23 e a infiltra&#231;&#227;o de c&#233;lulas T produtoras de IL&#8208;17 diminu&#237;ram em camundongos com defici&#234;ncia de CARD14&#46;<a class="elsevierStyleCrossRef" href="#bib0395"><span class="elsevierStyleSup">38</span></a> O estudo tamb&#233;m mostrou que as altera&#231;&#245;es inflamat&#243;rias psoriasiformes da pele eram menores em camundongos com defici&#234;ncia de CARD14&#44; sugeriu o poss&#237;vel papel imunol&#243;gico inflamat&#243;rio da CARD14 na patog&#234;nese da psor&#237;ase&#46;<a class="elsevierStyleCrossRef" href="#bib0395"><span class="elsevierStyleSup">38</span></a> Al&#233;m do PSORS1 e PSORS2&#44; muitos <span class="elsevierStyleItalic">loci</span> de suscetibilidade &#224; psor&#237;ase foram identificados com estudos de associa&#231;&#227;o ampla do genoma &#40;<span class="elsevierStyleItalic">genome&#8208;wide association studies</span> &#91;GWAS&#93;&#41;&#46; Tsoi et al&#46; fizeram uma metan&#225;lise de GWAS e identificaram 16 novos locais de suscetibilidade que regulam I&#8208;&#954;B quinase&#47;via NF&#8208;&#954;B e citotoxicidade e que respondem a est&#237;mulos externos e diferencia&#231;&#227;o de leuc&#243;citos&#46;<a class="elsevierStyleCrossRef" href="#bib0400"><span class="elsevierStyleSup">39</span></a> Al&#233;m dessas varia&#231;&#245;es gen&#233;ticas&#44; tamb&#233;m foram identificadas algumas muta&#231;&#245;es e polimorfismos espec&#237;ficos do subtipo&#46; Li et al&#46; demonstraram que o polimorfismo no gene antagonista do receptor de IL&#8208;36 &#40;IL36RN&#41; estava associado ao aumento do risco de psor&#237;ase pustulosa&#46;<a class="elsevierStyleCrossRef" href="#bib0405"><span class="elsevierStyleSup">40</span></a> Twelves et al&#46; investigaram as frequ&#234;ncias de muta&#231;&#227;o IL36RN entre diferentes subtipos de psor&#237;ase pustulosa e observaram que as muta&#231;&#245;es IL36RN eram mais frequentes entre pacientes com psor&#237;ase pustulosa generalizada&#46;<a class="elsevierStyleCrossRef" href="#bib0410"><span class="elsevierStyleSup">41</span></a> Estudos com diferentes antecedentes gen&#233;ticos em diferentes subtipos de psor&#237;ase sugerem que a PsnV pode ser uma doen&#231;a diferente&#44; e n&#227;o um subtipo de psor&#237;ase&#44; o que &#233; consistente com os presentes resultados&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">No presente estudo&#44; n&#227;o foi observada associa&#231;&#227;o entre o polimorfismo CYP2J2 e as caracter&#237;sticas cl&#237;nicas da psor&#237;ase&#46; A maioria dos pacientes com psor&#237;ase inclu&#237;dos no estudo estava em tratamento&#46; Com o tratamento&#44; as principais caracter&#237;sticas cl&#237;nicas&#44; como PASI&#44; comprometimento das unhas&#44; artralgia e artrite podem ser modificadas&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">Uma das limita&#231;&#245;es deste estudo &#233; que ele n&#227;o verificou as concentra&#231;&#245;es de EET e sua associa&#231;&#227;o com o polimorfismo do CYP2J2&#46; O polimorfismo do CYP2J2 pode contribuir para o processo inflamat&#243;rio e a patog&#234;nese da psor&#237;ase pela altera&#231;&#227;o das concentra&#231;&#245;es de ETT&#59; por&#233;m&#44; mais estudos s&#227;o necess&#225;rios para compreender a rela&#231;&#227;o entre psor&#237;ase e polimorfismo do CYP&#8208;ETT&#46; Outra limita&#231;&#227;o foi o n&#250;mero restrito de pacientes com psor&#237;ase com comorbidades cardiovasculares&#46; O presente estudo n&#227;o demonstrou rela&#231;&#227;o entre o polimorfismo do CYP e as comorbidades&#44; mas isso pode ser devido ao erro do tipo II &#40;beta&#41;&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">A base gen&#233;tica da psor&#237;ase &#233; complexa e difere entre os grupos &#233;tnicos e os subtipos de psor&#237;ase&#46; O polimorfismo CPY &#8211; como outros polimorfismos &#8211; pode variar entre os grupos &#233;tnicos&#46; Para generalizar os presentes resultados&#44; s&#227;o necess&#225;rios estudos adicionais com diferentes grupos &#233;tnicos e diferentes subtipos de psor&#237;ase&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Suporte financeiro</span><p id="par0105" class="elsevierStylePara elsevierViewall">Bolsa de pesquisa da Sociedade Turca de Dermatologia &#40;2017&#47;53&#41;&#46;</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Contribui&#231;&#227;o dos autores</span><p id="par0110" class="elsevierStylePara elsevierViewall">Y&#305;ld&#305;z Hayran&#58; An&#225;lise estat&#237;stica&#59; aprova&#231;&#227;o da vers&#227;o final do manuscrito&#59; concep&#231;&#227;o e planejamento do estudo&#59; elabora&#231;&#227;o e reda&#231;&#227;o do manuscrito&#59; obten&#231;&#227;o&#44; an&#225;lise e interpreta&#231;&#227;o dos dados&#59; participa&#231;&#227;o efetiva na orienta&#231;&#227;o da pesquisa&#59; participa&#231;&#227;o intelectual em conduta proped&#234;utica e&#47;ou terap&#234;utica de casos estudados&#59; revis&#227;o cr&#237;tica da literatura&#59; revis&#227;o cr&#237;tica do manuscrito&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">Nuran All&#305;&#58; Aprova&#231;&#227;o da vers&#227;o final do manuscrito&#59; revis&#227;o cr&#237;tica do manuscrito&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">P&#305;nar &#304;ncel Uysal&#58; Elabora&#231;&#227;o e reda&#231;&#227;o do manuscrito&#59; obten&#231;&#227;o&#44; an&#225;lise e interpreta&#231;&#227;o dos dados&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">Tuba &#199;andar&#58; Participa&#231;&#227;o efetiva na orienta&#231;&#227;o da pesquisa&#59; revis&#227;o cr&#237;tica do manuscrito&#46;</p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Conflitos de interesse</span><p id="par0130" 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">O citocromo P450 &#40;CYP&#41; 2J2 &#233; principalmente expresso em tecidos extra&#8208;hep&#225;ticos&#46; Ele metaboliza o &#225;cido araquid&#244;nico &#40;AA&#41; em &#225;cidos epoxieicosatrienoicos &#40;EETs&#41;&#44; com v&#225;rios efeitos cardioprotetores e anti&#8208;inflamat&#243;rios&#46; O polimorfismo do CYP2J2 foi identificado como um fator de risco para doen&#231;as cardiovasculares&#44; mas sua associa&#231;&#227;o com a psor&#237;ase permanece desconhecida&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Objetivo</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Avaliar se o polimorfismo do CYP2J2 &#233; um fator de risco para psor&#237;ase em uma popula&#231;&#227;o turca&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">M&#233;todos</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">O estudo incluiu 94 pacientes com psor&#237;ase e 100 controles saud&#225;veis&#44; pareados por idade e sexo&#46; Caracter&#237;sticas demogr&#225;ficas e cl&#237;nicas detalhadas foram registradas e os escores do &#205;ndice de &#193;rea e Gravidade da Psor&#237;ase &#40;PASI&#44; do ingl&#234;s <span class="elsevierStyleItalic">Psoriasis Area and Severity Index</span>&#41; foram calculados para pacientes com psor&#237;ase&#46; Amostras de sangue venoso foram coletadas de todos os participantes e o polimorfismo CYP2J2 50G<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>T &#40;rs890293&#41; foi analisado por rea&#231;&#227;o em cadeia da polimerase &#40;PCR&#41;&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Resultados</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">As frequ&#234;ncias do alelo T e do gen&#243;tipo TT<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>GT aumentaram em pacientes com psor&#237;ase vulgar &#40;PsV&#41; em compara&#231;&#227;o ao grupo controle &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;024 e p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;029&#44; respectivamente&#59; OR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>2&#44;82&#59; IC 95&#37;&#58;&#160;1&#44;11&#8211;7&#44;15&#41;&#46; N&#227;o foi identificada associa&#231;&#227;o entre o polimorfismo do CYP2J2 e as caracter&#237;sticas cl&#237;nicas da psor&#237;ase&#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">Um n&#250;mero reduzido de pacientes foi inclu&#237;do no estudo&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Conclus&#227;o</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">O polimorfismo CYP2J2 50G<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>T &#40;rs890293&#41; foi associado a um risco aumentado de PsV na popula&#231;&#227;o turca&#46;</p></span>"
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        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0015">Como citar este artigo&#58; Hayran Y&#44; All&#305; N&#44; Uysal P&#304;&#44; &#199;andar T&#46; Association of CYP2J2 polymorphism with susceptibility to psoriasis in Turkish population&#58; a case&#8208;control study&#46; An Bras Dermatol&#46; 2020&#59;95&#58;25&#8211;31&#46;</p>"
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      1 => array:2 [
        "etiqueta" => "&#9734;&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0020">Trabalho realizado no Departamento de Dermatologia&#44; Ankara Numune Training and Research Hospital&#44; Ankara&#44; Turquia&#46;</p>"
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">93 &#40;98&#44;9&#41;&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\ttable-entry\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t\ttable-entry\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 ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">0&#44;029&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">2&#44;35 &#40;0&#44;96&#63;5&#44;8&#41;&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\ttop\n
                  \t\t\t\t">2&#44;82 &#40;1&#44;11&#63;7&#44;15&#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">GG&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">78 &#40;82&#44;97&#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">57 &#40;80&#44;2&#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">92 &#40;92&#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
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                  \t\t\t\t">21&#44;4&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Doen&#231;as internas associadas e presen&#231;a de comorbidades</span>&nbsp;\t\t\t\t\t\t\n
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          "pt" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Caracter&#237;sticas demogr&#225;ficas e caracter&#237;sticas da doen&#231;a em pacientes com psor&#237;ase com gen&#243;tipo GG e gen&#243;tipo GT<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>TT</p>"
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                      "doi" => "10.1046/j.1365-2230.2001.00832.x"
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                            3 => "T&#46; Nijsten"
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                        "paginaFinal" => "11255"
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ISSN: 26662752
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