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incluindo doen&#231;as cardiovasculares&#44; diabetes e depress&#227;o&#44; e revisar op&#231;&#245;es de tratamento precoce&#46; Embora a complexa etiologia mediada imunologicamente ainda n&#227;o tenha sido totalmente elucidada&#44; a descoberta do eixo interleucina &#40;IL&#41;&#8208;23&#47;IL&#8208;17&#44; que &#233; importante na fisiopatologia da psor&#237;ase&#44; mudou a perspectiva nas op&#231;&#245;es de tratamento da doen&#231;a e atraiu aten&#231;&#227;o para a fam&#237;lia IL&#8208;17&#44; um dos mediadores importantes nessa via&#46;<a class="elsevierStyleCrossRefs" href="#bib0190"><span class="elsevierStyleSup">4&#8211;6</span></a> IL&#8208;17A e IL&#8208;17F&#44; que s&#227;o membros da fam&#237;lia IL&#8208;17 e t&#234;m aproximadamente 50&#37; de homologia estrutural&#44; desempenham papel central na patog&#234;nese da psor&#237;ase e ambas t&#234;m sido associadas a doen&#231;as inflamat&#243;rias imunomediadas&#44; incluindo a psor&#237;ase&#46;<a class="elsevierStyleCrossRefs" href="#bib0205"><span class="elsevierStyleSup">7&#8211;10</span></a> Tanto a IL&#8208;17A quanto a IL&#8208;17F atuam na regula&#231;&#227;o positiva da resposta inflamat&#243;ria&#44; mostrando intera&#231;&#245;es complexas com citocinas pr&#243;&#8208;inflamat&#243;rias&#46;<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">11</span></a> Relatos de n&#237;veis aumentados de mRNA de IL&#8208;17A e IL&#8208;17F no l&#237;quido sinovial de pacientes com artrite psori&#225;sica apoiam essa dupla associa&#231;&#227;o&#46;<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">12</span></a> Os agentes bloqueadores de IL&#8208;17A s&#227;o amplamente aceitos no tratamento da psor&#237;ase&#44; mas a diferen&#231;a nas respostas individuais ao tratamento e a diminui&#231;&#227;o de resposta ao longo do tempo levaram &#224; formula&#231;&#227;o de op&#231;&#245;es alternativas de tratamento&#44; como o bimequizumabe&#44; que emergiu como nova estrat&#233;gia que tem como alvo tanto IL&#8208;17A quanto IL&#8208;17F&#46; Com base em dados de estudos cl&#237;nicos e experimentais sobre essa nova estrat&#233;gia de tratamento&#44; pode&#8208;se afirmar que o duplo bloqueio proporciona melhora dos sintomas da doen&#231;a em pouco tempo&#44; e melhor resposta anti&#8208;inflamat&#243;ria &#233; obtida na regula&#231;&#227;o de genes relacionados ao processo inflamat&#243;rio em compara&#231;&#227;o aos tratamentos direcionados apenas &#224; IL&#8208;17A&#46;<a class="elsevierStyleCrossRefs" href="#bib0230"><span class="elsevierStyleSup">12&#8211;15</span></a> Desse modo&#44; parece poss&#237;vel dizer que o <span class="elsevierStyleItalic">locus</span> do gene IL&#8208;17F desempenha papel como citocina central na imunopatog&#234;nese da psor&#237;ase&#46; Al&#233;m disso&#44; a demonstra&#231;&#227;o do aumento da produ&#231;&#227;o de IL&#8208;6 e IL&#8208;8 pela indu&#231;&#227;o de IL&#8208;17F em les&#245;es cut&#226;neas de pacientes com psor&#237;ase endossou mais uma vez o papel da IL&#8208;17F na patog&#234;nese da psor&#237;ase&#46;<a class="elsevierStyleCrossRefs" href="#bib0250"><span class="elsevierStyleSup">16&#44;17</span></a> Por fim&#44; o relato de que camundongos <span class="elsevierStyleItalic">knockout</span> para IL&#8208;17F apresentam maior resist&#234;ncia &#224; psor&#237;ase em compara&#231;&#227;o com camundongos <span class="elsevierStyleItalic">knockout</span> para IL&#8208;17A indica que IL&#8208;17F est&#225; intimamente relacionada &#224; psor&#237;ase&#46;<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">18</span></a> Apesar de seu papel central na patog&#234;nese da psor&#237;ase&#44; o n&#250;mero de estudos que investigam o efeito das varia&#231;&#245;es no <span class="elsevierStyleItalic">locus</span> do gene IL&#8208;7F na patog&#234;nese da doen&#231;a &#233; bastante limitado e&#44; al&#233;m disso&#44; n&#227;o existem dados relacionados com essa quest&#227;o na sociedade turca&#46; Os componentes gen&#233;ticos podem afetar n&#227;o apenas a suscetibilidade &#224; doen&#231;a&#44; mas tamb&#233;m o tipo cl&#237;nico&#44; a idade de in&#237;cio&#44; a gravidade e at&#233; 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201 pacientes com psor&#237;ase atendidos no Giresun University A&#46; &#304;lhan &#214;zdemir Training and Research Hospital entre 2019 e 2021&#44; com diagn&#243;stico cl&#237;nico ou histopatol&#243;gico&#44; foram inclu&#237;dos no grupo de estudo&#46; Como grupo controle&#44; foram inclu&#237;dos 402 indiv&#237;duos atendidos no ambulat&#243;rio de dermatologia com doen&#231;a dermatol&#243;gica&#44; pareados por idade &#40;sem evid&#234;ncia cl&#237;nica de psor&#237;ase ou outras doen&#231;as autoimunes&#41;&#46; Esses indiv&#237;duos n&#227;o tinham hist&#243;rico de psor&#237;ase ou qualquer doen&#231;a inflamat&#243;ria cr&#244;nica&#46; As caracter&#237;sticas demogr&#225;ficas e cl&#237;nicas dos pacientes com psor&#237;ase e do grupo controle foram registradas em planilhas sincronizadas para uso posterior&#46; Artrite psori&#225;sica foi investigada em todos os pacientes&#46; Crian&#231;as &#40;idade &#60; 18&#59; n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>8&#41;&#44; participantes gr&#225;vidas e lactantes &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>3&#41; e participantes &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>13&#41; com hist&#243;rico de qualquer doen&#231;a imunol&#243;gica ou inflamat&#243;ria foram exclu&#237;dos do estudo&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">An&#225;lise do gen&#243;tipo da IL&#8208;17F rs763780</span><p id="par0015" class="elsevierStylePara elsevierViewall">As an&#225;lises de DNA foram realizadas com <span class="elsevierStyleItalic">kit</span> comercial &#40;Roche High Pure Isolation Kit&#44; Alemanha&#41; utilizando sangue perif&#233;rico coletado dos pacientes do estudo&#44; e os n&#237;veis de DNA foram calculados determinando sua pureza e armazenados a &#43;4<span class="elsevierStyleHsp" style=""></span>&#176;C at&#233; o momento do estudo&#46; As varia&#231;&#245;es al&#233;licas IL&#8208;17F rs763780 foram genotipadas com o m&#233;todo PCR em tempo real e teste quantitativo bidirecional TaqMan 5&#8217; Allelic Discrimination Test &#40;Applied Biosystems&#44; Foster City&#44; CA&#41; utilizando protocolos estabelecidos de acordo com as instru&#231;&#245;es do fabricante&#46; A amplifica&#231;&#227;o por PCR foi realizada a 95<span class="elsevierStyleHsp" style=""></span>&#176;C por 10 minutos&#44; a 95<span class="elsevierStyleHsp" style=""></span>&#176;C por 15 segundos&#44; a 55<span class="elsevierStyleHsp" style=""></span>&#176;C por 1 minuto e a 72<span class="elsevierStyleHsp" style=""></span>&#176;C por 1 minuto em 45 ciclos&#46; Para controle&#44; 10&#37; das amostras selecionadas aleatoriamente foram genotipadas em duplicata&#44; e a precis&#227;o dos resultados foi novamente confirmada&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">An&#225;lise estat&#237;stica</span><p id="par0020" class="elsevierStylePara elsevierViewall">A an&#225;lise estat&#237;stica deste estudo foi realizada utilizando o programa SPSS 20&#46; A signific&#226;ncia estat&#237;stica foi considerada como p &#60; 0&#44;05&#46; Alelos e frequ&#234;ncias genot&#237;picas foram calculados por contagem direta&#46; As distribui&#231;&#245;es genot&#237;picas nos grupos de estudo foram analisadas por compatibilidade com o equil&#237;brio de Hardy&#8208;Weinberg &#40;HWE&#44; do ingl&#234;s <span class="elsevierStyleItalic">Hardy&#8208;Weinberg equilibrium</span>&#41;&#46; O teste de Qui&#8208;Quadrado &#40;&#967;<span class="elsevierStyleSup">2</span>&#41; foi utilizado para avaliar as diferen&#231;as intergrupos na frequ&#234;ncia de gen&#243;tipo e alelos&#46; <span class="elsevierStyleItalic">Odds ratio</span> &#40;OR&#41; e intervalo de confian&#231;a de 95&#37; &#40;IC95&#37;&#41; s&#227;o utilizados para determinar o fator de risco entre os grupos&#46; Para determinar a rela&#231;&#227;o entre o risco de psor&#237;ase e a presen&#231;a do alelo IL&#8208;17F rs763780<span class="elsevierStyleHsp" style=""></span>C&#44; foram realizados modelo de regress&#227;o log&#237;stica bin&#225;ria e an&#225;lise de regress&#227;o multivariada&#44; com signific&#226;ncia de p &#60; 0&#44;05&#46; A psor&#237;ase foi utilizada como vari&#225;vel dependente&#46;</p></span></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Resultados</span><p id="par0025" class="elsevierStylePara elsevierViewall">As informa&#231;&#245;es das caracter&#237;sticas demogr&#225;ficas dos grupos de trabalho s&#227;o mostradas na <a class="elsevierStyleCrossRef" href="#tbl0005">tabela 1</a>&#46; Artrite psori&#225;sica foi observada em 46 dos pacientes com psor&#237;ase&#44; enquanto nenhum sinal de artrite psori&#225;sica foi encontrado em 155 pacientes&#46; Quando os pacientes foram divididos em dois grupos de acordo com a idade de in&#237;cio da psor&#237;ase&#44; o n&#250;mero de pacientes com psor&#237;ase de in&#237;cio precoce &#40;idade &#8804; 40&#41; foi de 132&#44; e o n&#250;mero de pacientes com psor&#237;ase de in&#237;cio tardio &#40;idade<span class="elsevierStyleHsp" style=""></span>&#62; 40&#41; foi de 69&#46; Trinta e cinco dos pacientes tinham hist&#243;ria de psor&#237;ase em parentes de primeiro grau e em 166 pacientes n&#227;o foi identificada hist&#243;ria de psor&#237;ase em parentes de primeiro grau&#46; O n&#250;mero de pacientes cujo escore PASI &#40;do ingl&#234;s <span class="elsevierStyleItalic">Psoriasis Area and Severity Index</span>&#41; era &#8804; 10 foi 28&#44; e o restante do grupo de psor&#237;ase&#44; 173 pacientes&#44; apresentou escore PASI<span class="elsevierStyleHsp" style=""></span>&#62; 10&#46; As distribui&#231;&#245;es genot&#237;picas e as fra&#231;&#245;es al&#233;licas das popula&#231;&#245;es de estudo s&#227;o apresentadas na <a class="elsevierStyleCrossRef" href="#tbl0010">tabela 2</a>&#46; Tanto o grupo de pacientes quanto o grupo controle mostraram compatibilidade com o HWE&#46; H&#225; diferen&#231;a estatisticamente significante entre os grupos de pacientes e controle em termos de distribui&#231;&#245;es genot&#237;picas &#40;p &#60; 0&#44;001&#41;&#46; Os gen&#243;tipos TC e CC foram mais representados no grupo de pacientes do que no grupo controle &#40;24&#44;9&#37; <span class="elsevierStyleItalic">vs</span>&#46; 10&#44;2&#37;&#59; 2&#44;0&#37; <span class="elsevierStyleItalic">vs</span>&#46; 0&#44;2&#37;&#44; respectivamente&#41;&#46; Al&#233;m disso&#44; o alelo variante C foi mais prevalente no grupo de pacientes e isso foi estatisticamente significante &#40;p &#60; 0&#44;001&#41;&#44; e a presen&#231;a do alelo C foi associada a um risco 3&#44;14 vezes maior de psor&#237;ase &#40;IC95&#37; 2&#44;015&#8208;24&#44;921&#41;&#46; Quando as distribui&#231;&#245;es genot&#237;picas no grupo de pacientes foram avaliadas em termos de hist&#243;ria familiar&#44; artrite psori&#225;sica&#44; idade de in&#237;cio e g&#234;nero&#44; n&#227;o foi observada diferen&#231;a estat&#237;stica &#40;dados n&#227;o mostrados&#41;&#46; Os resultados da an&#225;lise de regress&#227;o log&#237;stica para comprovar a rela&#231;&#227;o entre psor&#237;ase e o alelo IL&#8208;17F C tamb&#233;m confirmaram que o alelo variante C aumenta o risco de psor&#237;ase &#40;p &#60; 0&#44;001&#59; IC95&#37; 2&#44;015&#8208;4&#44;491&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0010"></elsevierMultimedia></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Discuss&#227;o</span><p id="par0030" class="elsevierStylePara elsevierViewall">Existem seis membros da fam&#237;lia IL&#8208;17 &#40;IL17A&#8208;IL17F&#41;&#44; que desempenham papel cr&#237;tico na patog&#234;nese da psor&#237;ase&#46;<a class="elsevierStyleCrossRefs" href="#bib0270"><span class="elsevierStyleSup">20&#8211;22</span></a> Os mais estudados s&#227;o IL&#8208;17A e IL&#8208;17F&#44; que t&#234;m fun&#231;&#245;es biol&#243;gicas semelhantes&#44; mostrando 50&#37; de homologia&#46; Ambos t&#234;m sido frequentemente associados a muitas doen&#231;as inflamat&#243;rias&#44; incluindo a psor&#237;ase&#46;<a class="elsevierStyleCrossRefs" href="#bib0285"><span class="elsevierStyleSup">23&#8211;25</span></a> Embora a IL&#8208;17A pare&#231;a desempenhar papel central na patog&#234;nese da psor&#237;ase&#44; estudos recentes relataram um n&#237;vel crescente de IL&#8208;17F na pele lesionada da psor&#237;ase&#44; al&#233;m da demonstra&#231;&#227;o de que IL&#8208;17F tem fun&#231;&#245;es semelhantes &#224;s de IL&#8208;17A e come&#231;ou&#8208;se a focar no poss&#237;vel papel cr&#237;tico de IL&#8208;17F na imunopatog&#234;nese da doen&#231;a&#46;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">26</span></a> Os resultados de um estudo recente de Bertelsen et al&#46; forneceram evid&#234;ncias de que IL&#8208;17F desempenha papel fundamental no eixo IL&#8208;23&#47;IL&#8208;17<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">26</span></a> e mostraram que a estimula&#231;&#227;o de IL&#8208;17F induz a express&#227;o de I&#954;B&#954;&#44; cujo papel cr&#237;tico na patog&#234;nese da psor&#237;ase foi demonstrado anteriormente<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">27</span></a> em queratin&#243;citos humanos&#44; alterando os n&#237;veis de mRNA e de prote&#237;na&#44; e desempenhando papel na regula&#231;&#227;o de muitos genes&#44; como os associados &#224; psor&#237;ase&#46;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">26</span></a> Outras evid&#234;ncias acumuladas mostram que a variante IL&#8208;17F rs763780 produz diferentes respostas medicamentosas &#224;s abordagens terap&#234;uticas&#46; Essa situa&#231;&#227;o destacou mais uma vez o papel cr&#237;tico da IL&#8208;17F na patog&#234;nese da psor&#237;ase&#46;<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">28</span></a> Os pesquisadores avaliaram a resposta PASI 75 em um grupo de estudo de 194 pacientes com psor&#237;ase e associaram o gen&#243;tipo IL17F rs763780 TT a melhor resposta ao tratamento com ustequinumabe&#46; Dados de outro estudo no qual ustequinumabe foi administrado tamb&#233;m relataram diminui&#231;&#227;o nos n&#237;veis de IL&#8208;17A e IL&#8208;17F na semana 24&#44; mas essa diminui&#231;&#227;o foi significante apenas entre IL&#8208;17F e placebos&#46;<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">29</span></a> Embora o papel da IL&#8208;17F na imunopatog&#234;nese da psor&#237;ase n&#227;o tenha sido totalmente esclarecido&#44; a determina&#231;&#227;o das variantes desse gene &#233; de grande import&#226;ncia em termos de cria&#231;&#227;o de op&#231;&#245;es de tratamento paciente&#8208;espec&#237;ficas&#46; No entanto&#44; h&#225; poucos estudos sobre esse assunto na literatura&#44; e a investiga&#231;&#227;o &#233; bastante limitada&#46; Um desses estudos&#44; de Kaur et al&#46;&#44; associou a variante IL&#8208;17F rs763780 ao aumento da suscetibilidade &#224; psor&#237;ase&#46;<a class="elsevierStyleCrossRef" href="#bib0320"><span class="elsevierStyleSup">30</span></a> No presente estudo&#44; foi observado que os gen&#243;tipos portadores do alelo variante prevaleciam no grupo de pacientes em compara&#231;&#227;o ao grupo controle&#44; o que &#233; semelhante aos dados de Kaur et al&#46; Al&#233;m disso&#44; os autores avaliaram que o alelo variante est&#225; associado a um risco 3&#44;1 vezes maior de psor&#237;ase&#46; Da mesma maneira&#44; Choi et al&#46;&#44; que definiram IL&#8208;17F como um novo <span class="elsevierStyleItalic">locus</span> de risco para psor&#237;ase&#44; relataram que os gen&#243;tipos portadores do alelo variante estavam mais amplamente representados no grupo de pacientes&#46;<a class="elsevierStyleCrossRef" href="#bib0325"><span class="elsevierStyleSup">31</span></a> Consistente com esses dados&#44; outro estudo em popula&#231;&#227;o coreana relatou que o gen&#243;tipo da variante homozig&#243;tica estava associado a um risco 3&#44;27 vezes maior de psor&#237;ase&#46;<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">32</span></a> Contudo os dados de estudos conduzidos em popula&#231;&#245;es japonesas e espanholas<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">33</span></a> n&#227;o relataram associa&#231;&#227;o entre a variante IL&#8208;17F rs763780 e psor&#237;ase&#46; Isso pode ser explicado pelo fato de que um gene depende de seu contexto gen&#244;mico e pode exibir diferentes padr&#245;es de express&#227;o em diferentes grupos &#233;tnicos&#46;<a class="elsevierStyleCrossRef" href="#bib0340"><span class="elsevierStyleSup">34</span></a> Com base nas informa&#231;&#245;es obtidas do presente estudo&#44; os autores enfatizam a rela&#231;&#227;o da IL&#8208;17F com a psor&#237;ase&#46; Al&#233;m disso&#44; tem&#8208;se a impress&#227;o de que a variante IL&#8208;17F rs763780 induziu suscetibilidade &#224; doen&#231;a pelo alelo C&#46; Como a psor&#237;ase apresenta muitas comorbidades&#44; &#233; importante determinar os grupos de risco e aplicar precocemente as op&#231;&#245;es de tratamento&#46; A variante IL&#8208;17F rs763780 pode ser recomendada como biomarcador apropriado pois tratamentos apropriados&#44; visando o alvo correto&#44; possibilitar&#227;o aos m&#233;dicos diminuir a morbidade na doen&#231;a&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Limita&#231;&#245;es</span><p id="par0035" class="elsevierStylePara elsevierViewall">O presente estudo tem algumas limita&#231;&#245;es&#46; A primeira delas &#233; o tamanho relativamente pequeno da amostra&#46; Um tamanho de amostra maior aumentaria o poder estat&#237;stico&#46; A segunda limita&#231;&#227;o &#233; que n&#227;o foi poss&#237;vel medir os n&#237;veis de express&#227;o de IL&#8208;17F&#46; No entanto&#44; o presente estudo chama a aten&#231;&#227;o para a import&#226;ncia da IL&#8208;17F que merece ser avaliada em um grupo amostral maior&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Conclus&#227;o</span><p id="par0040" class="elsevierStylePara elsevierViewall">Com base nas informa&#231;&#245;es obtidas no presente estudo&#44; os autores enfatizam a rela&#231;&#227;o da IL&#8208;17F com a psor&#237;ase&#46; Al&#233;m disso&#44; os gen&#243;tipos IL&#8208;17F rs763780 TC e CC e o alelo C est&#227;o associados ao aumento do risco de psor&#237;ase na popula&#231;&#227;o turca&#44; de acordo com essa amostra&#46; Como a psor&#237;ase apresenta elevadas comorbidades&#44; &#233; importante determinar os grupos de risco e aplicar precocemente as op&#231;&#245;es de tratamento&#46; A variante IL&#8208;17F rs763780 pode ser recomendada como biomarcador apropriado pois tratamentos apropriados&#44; visando o alvo correto&#44; possibilitar&#227;o aos m&#233;dicos diminuir a morbidade na doen&#231;a&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Suporte financeiro</span><p id="par0045" class="elsevierStylePara elsevierViewall">O presente estudo foi financiado por uma bolsa da Scientific Research Projects Coordination Unit&#44; Giresun University &#40;Projeto n&#176; SA&#286;&#8208;BAP&#8208;A&#8208;270220&#8208;07&#41;&#46;</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Contribui&#231;&#227;o dos autores</span><p id="par0050" class="elsevierStylePara elsevierViewall">Ay&#351;eg&#252;l Ba&#351;ak Akadam&#8208;Teker&#58; Concep&#231;&#227;o do estudo&#44; fornecimento de amostras&#44; an&#225;lise dos dados&#44; pesquisa na literatura&#44; reda&#231;&#227;o do artigo e realiza&#231;&#227;o do trabalho laboratorial&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">Burak Ak&#351;an&#58; Fornecimento de amostras&#44; an&#225;lise dos dados e pesquisa na literatura&#46;</p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Conflito de interesses</span><p id="par0060" class="elsevierStylePara elsevierViewall">Nenhum&#46;</p></span></span>"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Fundamentos</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">A psor&#237;ase representa fen&#243;tipo inflamat&#243;rio cr&#244;nico moldado por intera&#231;&#245;es gen&#233;ticas&#44; caracterizado pela hiperprolifera&#231;&#227;o de queratin&#243;citos e comumente afetando a pele e as articula&#231;&#245;es&#46; Estudos experimentais e cl&#237;nicos sugerem que o <span class="elsevierStyleItalic">locus</span> do gene IL&#8208;17F desempenhe papel como citocina central na imunopatog&#234;nese da psor&#237;ase&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Objetivos</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Com base no papel central da IL&#8208;17F na patog&#234;nese da psor&#237;ase&#44; levantou&#8208;se a hip&#243;tese de que varia&#231;&#245;es nesse gene poderiam afetar a suscetibilidade e gravidade dessa doen&#231;a&#46; Portanto&#44; o presente estudo pretende analisar se a variante IL&#8208;17F rs763780 tem efeito na patog&#234;nese da psor&#237;ase na popula&#231;&#227;o turca&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">M&#233;todo</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Neste estudo de caso&#8208;controle&#44; o grupo de estudo consistiu em 603 pessoas &#40;201 pacientes com psor&#237;ase &#8211; 73 homens e 128 mulheres&#59; e 402 controles &#8211; 146 homens e 256 mulheres&#41; genotipados em termos do polimorfismo IL&#8208;17F rs763780 com o TaqMan 5&#8217; Allelic Discrimination Test&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Resultados</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">As distribui&#231;&#245;es genot&#237;picas do polimorfismo IL&#8208;17F rs763780 entre os grupos de pacientes e controle foram estatisticamente diferentes&#44; e os gen&#243;tipos TC &#40;gen&#243;tipo heterozigoto&#41; e CC &#40;gen&#243;tipo mutante homozigoto&#41; foram mais representados no grupo de pacientes do que no grupo controle &#40;24&#44;9&#37; <span class="elsevierStyleItalic">vs</span>&#46; 10&#44;2&#37;&#59; 2&#44;0&#37; <span class="elsevierStyleItalic">vs</span>&#46; 0&#44;2&#37;&#44; respectivamente&#41;&#46; Al&#233;m disso&#44; o alelo variante C foi mais prevalente no grupo de pacientes e isso foi estatisticamente significante &#40;p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41;&#44; e a presen&#231;a do alelo C foi associada a um risco 3&#44;14 vezes maior de psor&#237;ase &#40;IC 95&#37; 2&#44;015&#8208;24&#44;921&#41;&#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">O presente estudo tem algumas limita&#231;&#245;es&#46; A primeira delas &#233; o tamanho relativamente pequeno da amostra&#46; A segunda &#233; que n&#227;o foi poss&#237;vel medir os n&#237;veis da express&#227;o de IL&#8208;17F&#46; No entanto&#44; os dados do estudo chamam a aten&#231;&#227;o para a import&#226;ncia da IL&#8208;17F&#44; indicando que merece ser avaliada em um grupo amostral maior&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Conclus&#227;o</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Os autores relatam que o gen&#243;tipo IL&#8208;17F rs763780 TC e CC e o alelo C est&#227;o associados ao aumento do risco de psor&#237;ase na popula&#231;&#227;o turca&#46;</p></span>"
        "secciones" => array:6 [
          0 => array:2 [
            "identificador" => "abst0005"
            "titulo" => "Fundamentos"
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          4 => array:2 [
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            "titulo" => "Limita&#231;&#245;es do estudo"
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          5 => array:2 [
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    "NotaPie" => array:2 [
      0 => array:2 [
        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Como citar este artigo&#58; Akadam&#8208;Teker AB&#44; Ak&#351;an B&#46; Association of IL&#8208;17F rs763780 polymorphism and risk of psoriasis in Turkish population&#58; a case&#8208;control study&#46; An Bras Dermatol&#46; 2024&#59;99&#58;357&#8211;61&#46;</p>"
      ]
      1 => array:2 [
        "etiqueta" => "&#9734;&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0010">Trabalho realizado no Departamento de Gen&#233;tica M&#233;dica e no Departamento de Doen&#231;as Cut&#226;neas&#44; Faculdade de Medicina&#44; Giresun University&#44; Giresun&#44; Turquia&#46;</p>"
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          "leyenda" => "<p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Os valores m&#233;dios foram comparados entre pacientes e controles por meio do teste <span class="elsevierStyleItalic">t</span> de Student&#46; Os dados qualitativos foram analisados pelo teste de Qui&#8208;Quadrado&#46;</p><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Os dados s&#227;o apresentados como m&#233;dia<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>DP e n &#40;&#37;&#41;&#46; Os valores em negrito foram estatisticamente significantes &#40;p &#60; 0&#44;05&#41;&#46;</p><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">NS&#44; n&#227;o significante&#44; PASI&#44; Psoriasis Area and Severity Index&#59; n&#44; n&#250;mero de amostras&#46;</p>"
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                        "tituloSerie" => "Expert Opin Emerg Drugs&#46;"
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Artigo original
Associação do polimorfismo IL‐17F rs763780 e risco de psoríase na população turca: estudo de caso controle
Ayşegül Başak Akadam-Tekera,
Corresponding author
aba2904@hotmail.com

Autor para correspondência.
, Burak Akşanb
a Departamento de Genética Médica, Faculdade de Medicina, Giresun University, Giresun, Turquia
b Departamento de Doenças Cutâneas, Faculdade de Medicina, Giresun University, Giresun, 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 representa fen&#243;tipo inflamat&#243;rio cr&#244;nico moldado por intera&#231;&#245;es gen&#233;ticas&#44; caracterizado pela hiperprolifera&#231;&#227;o de queratin&#243;citos e comumente afetando a pele e as articula&#231;&#245;es&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">1</span></a> A psor&#237;ase afeta 1&#37; a 3&#37; da popula&#231;&#227;o mundial&#44; e os pacientes tamb&#233;m t&#234;m que lidar com os problemas psicol&#243;gicos e fisiol&#243;gicos causados pela doen&#231;a&#46;<a class="elsevierStyleCrossRefs" href="#bib0180"><span class="elsevierStyleSup">2&#44;3</span></a> &#201; muito importante identificar indiv&#237;duos em risco de contrair psor&#237;ase com comorbidades significantes&#44; incluindo doen&#231;as cardiovasculares&#44; diabetes e depress&#227;o&#44; e revisar op&#231;&#245;es de tratamento precoce&#46; Embora a complexa etiologia mediada imunologicamente ainda n&#227;o tenha sido totalmente elucidada&#44; a descoberta do eixo interleucina &#40;IL&#41;&#8208;23&#47;IL&#8208;17&#44; que &#233; importante na fisiopatologia da psor&#237;ase&#44; mudou a perspectiva nas op&#231;&#245;es de tratamento da doen&#231;a e atraiu aten&#231;&#227;o para a fam&#237;lia IL&#8208;17&#44; um dos mediadores importantes nessa via&#46;<a class="elsevierStyleCrossRefs" href="#bib0190"><span class="elsevierStyleSup">4&#8211;6</span></a> IL&#8208;17A e IL&#8208;17F&#44; que s&#227;o membros da fam&#237;lia IL&#8208;17 e t&#234;m aproximadamente 50&#37; de homologia estrutural&#44; desempenham papel central na patog&#234;nese da psor&#237;ase e ambas t&#234;m sido associadas a doen&#231;as inflamat&#243;rias imunomediadas&#44; incluindo a psor&#237;ase&#46;<a class="elsevierStyleCrossRefs" href="#bib0205"><span class="elsevierStyleSup">7&#8211;10</span></a> Tanto a IL&#8208;17A quanto a IL&#8208;17F atuam na regula&#231;&#227;o positiva da resposta inflamat&#243;ria&#44; mostrando intera&#231;&#245;es complexas com citocinas pr&#243;&#8208;inflamat&#243;rias&#46;<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">11</span></a> Relatos de n&#237;veis aumentados de mRNA de IL&#8208;17A e IL&#8208;17F no l&#237;quido sinovial de pacientes com artrite psori&#225;sica apoiam essa dupla associa&#231;&#227;o&#46;<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">12</span></a> Os agentes bloqueadores de IL&#8208;17A s&#227;o amplamente aceitos no tratamento da psor&#237;ase&#44; mas a diferen&#231;a nas respostas individuais ao tratamento e a diminui&#231;&#227;o de resposta ao longo do tempo levaram &#224; formula&#231;&#227;o de op&#231;&#245;es alternativas de tratamento&#44; como o bimequizumabe&#44; que emergiu como nova estrat&#233;gia que tem como alvo tanto IL&#8208;17A quanto IL&#8208;17F&#46; Com base em dados de estudos cl&#237;nicos e experimentais sobre essa nova estrat&#233;gia de tratamento&#44; pode&#8208;se afirmar que o duplo bloqueio proporciona melhora dos sintomas da doen&#231;a em pouco tempo&#44; e melhor resposta anti&#8208;inflamat&#243;ria &#233; obtida na regula&#231;&#227;o de genes relacionados ao processo inflamat&#243;rio em compara&#231;&#227;o aos tratamentos direcionados apenas &#224; IL&#8208;17A&#46;<a class="elsevierStyleCrossRefs" href="#bib0230"><span class="elsevierStyleSup">12&#8211;15</span></a> Desse modo&#44; parece poss&#237;vel dizer que o <span class="elsevierStyleItalic">locus</span> do gene IL&#8208;17F desempenha papel como citocina central na imunopatog&#234;nese da psor&#237;ase&#46; Al&#233;m disso&#44; a demonstra&#231;&#227;o do aumento da produ&#231;&#227;o de IL&#8208;6 e IL&#8208;8 pela indu&#231;&#227;o de IL&#8208;17F em les&#245;es cut&#226;neas de pacientes com psor&#237;ase endossou mais uma vez o papel da IL&#8208;17F na patog&#234;nese da psor&#237;ase&#46;<a class="elsevierStyleCrossRefs" href="#bib0250"><span class="elsevierStyleSup">16&#44;17</span></a> Por fim&#44; o relato de que camundongos <span class="elsevierStyleItalic">knockout</span> para IL&#8208;17F apresentam maior resist&#234;ncia &#224; psor&#237;ase em compara&#231;&#227;o com camundongos <span class="elsevierStyleItalic">knockout</span> para IL&#8208;17A indica que IL&#8208;17F est&#225; intimamente relacionada &#224; psor&#237;ase&#46;<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">18</span></a> Apesar de seu papel central na patog&#234;nese da psor&#237;ase&#44; o n&#250;mero de estudos que investigam o efeito das varia&#231;&#245;es no <span class="elsevierStyleItalic">locus</span> do gene IL&#8208;7F na patog&#234;nese da doen&#231;a &#233; bastante limitado e&#44; al&#233;m disso&#44; n&#227;o existem dados relacionados com essa quest&#227;o na sociedade turca&#46; Os componentes gen&#233;ticos podem afetar n&#227;o apenas a suscetibilidade &#224; doen&#231;a&#44; mas tamb&#233;m o tipo cl&#237;nico&#44; a idade de in&#237;cio&#44; a gravidade e at&#233; mesmo o risco de artrite psori&#225;sica&#46; Portanto&#44; o objetivo do presente estudo foi investigar a poss&#237;vel rela&#231;&#227;o da variante IL&#8208;17F rs763780 com a doen&#231;a&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">M&#233;todos</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Desenho do estudo</span><p id="par0010" class="elsevierStylePara elsevierViewall">O presente protocolo de estudo foi aprovado pelo Comit&#234; de &#201;tica da Faculdade de Medicina da Giresun University &#40;n&#250;mero do comit&#234; de &#233;tica&#58; KAEK&#8208;115&#41; e consentimento informado por escrito foi obtido de todos os pacientes&#46; Todos os procedimentos realizados neste estudo estavam em conformidade com os padr&#245;es &#233;ticos do comit&#234; de pesquisa institucional e&#47;ou nacional e com a Declara&#231;&#227;o de Helsinque da World Medical Association&#46;<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">19</span></a> Neste estudo&#44; 201 pacientes com psor&#237;ase atendidos no Giresun University A&#46; &#304;lhan &#214;zdemir Training and Research Hospital entre 2019 e 2021&#44; com diagn&#243;stico cl&#237;nico ou histopatol&#243;gico&#44; foram inclu&#237;dos no grupo de estudo&#46; Como grupo controle&#44; foram inclu&#237;dos 402 indiv&#237;duos atendidos no ambulat&#243;rio de dermatologia com doen&#231;a dermatol&#243;gica&#44; pareados por idade &#40;sem evid&#234;ncia cl&#237;nica de psor&#237;ase ou outras doen&#231;as autoimunes&#41;&#46; Esses indiv&#237;duos n&#227;o tinham hist&#243;rico de psor&#237;ase ou qualquer doen&#231;a inflamat&#243;ria cr&#244;nica&#46; As caracter&#237;sticas demogr&#225;ficas e cl&#237;nicas dos pacientes com psor&#237;ase e do grupo controle foram registradas em planilhas sincronizadas para uso posterior&#46; Artrite psori&#225;sica foi investigada em todos os pacientes&#46; Crian&#231;as &#40;idade &#60; 18&#59; n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>8&#41;&#44; participantes gr&#225;vidas e lactantes &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>3&#41; e participantes &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>13&#41; com hist&#243;rico de qualquer doen&#231;a imunol&#243;gica ou inflamat&#243;ria foram exclu&#237;dos do estudo&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">An&#225;lise do gen&#243;tipo da IL&#8208;17F rs763780</span><p id="par0015" class="elsevierStylePara elsevierViewall">As an&#225;lises de DNA foram realizadas com <span class="elsevierStyleItalic">kit</span> comercial &#40;Roche High Pure Isolation Kit&#44; Alemanha&#41; utilizando sangue perif&#233;rico coletado dos pacientes do estudo&#44; e os n&#237;veis de DNA foram calculados determinando sua pureza e armazenados a &#43;4<span class="elsevierStyleHsp" style=""></span>&#176;C at&#233; o momento do estudo&#46; As varia&#231;&#245;es al&#233;licas IL&#8208;17F rs763780 foram genotipadas com o m&#233;todo PCR em tempo real e teste quantitativo bidirecional TaqMan 5&#8217; Allelic Discrimination Test &#40;Applied Biosystems&#44; Foster City&#44; CA&#41; utilizando protocolos estabelecidos de acordo com as instru&#231;&#245;es do fabricante&#46; A amplifica&#231;&#227;o por PCR foi realizada a 95<span class="elsevierStyleHsp" style=""></span>&#176;C por 10 minutos&#44; a 95<span class="elsevierStyleHsp" style=""></span>&#176;C por 15 segundos&#44; a 55<span class="elsevierStyleHsp" style=""></span>&#176;C por 1 minuto e a 72<span class="elsevierStyleHsp" style=""></span>&#176;C por 1 minuto em 45 ciclos&#46; Para controle&#44; 10&#37; das amostras selecionadas aleatoriamente foram genotipadas em duplicata&#44; e a precis&#227;o dos resultados foi novamente confirmada&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">An&#225;lise estat&#237;stica</span><p id="par0020" class="elsevierStylePara elsevierViewall">A an&#225;lise estat&#237;stica deste estudo foi realizada utilizando o programa SPSS 20&#46; A signific&#226;ncia estat&#237;stica foi considerada como p &#60; 0&#44;05&#46; Alelos e frequ&#234;ncias genot&#237;picas foram calculados por contagem direta&#46; As distribui&#231;&#245;es genot&#237;picas nos grupos de estudo foram analisadas por compatibilidade com o equil&#237;brio de Hardy&#8208;Weinberg &#40;HWE&#44; do ingl&#234;s <span class="elsevierStyleItalic">Hardy&#8208;Weinberg equilibrium</span>&#41;&#46; O teste de Qui&#8208;Quadrado &#40;&#967;<span class="elsevierStyleSup">2</span>&#41; foi utilizado para avaliar as diferen&#231;as intergrupos na frequ&#234;ncia de gen&#243;tipo e alelos&#46; <span class="elsevierStyleItalic">Odds ratio</span> &#40;OR&#41; e intervalo de confian&#231;a de 95&#37; &#40;IC95&#37;&#41; s&#227;o utilizados para determinar o fator de risco entre os grupos&#46; Para determinar a rela&#231;&#227;o entre o risco de psor&#237;ase e a presen&#231;a do alelo IL&#8208;17F rs763780<span class="elsevierStyleHsp" style=""></span>C&#44; foram realizados modelo de regress&#227;o log&#237;stica bin&#225;ria e an&#225;lise de regress&#227;o multivariada&#44; com signific&#226;ncia de p &#60; 0&#44;05&#46; A psor&#237;ase foi utilizada como vari&#225;vel dependente&#46;</p></span></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Resultados</span><p id="par0025" class="elsevierStylePara elsevierViewall">As informa&#231;&#245;es das caracter&#237;sticas demogr&#225;ficas dos grupos de trabalho s&#227;o mostradas na <a class="elsevierStyleCrossRef" href="#tbl0005">tabela 1</a>&#46; Artrite psori&#225;sica foi observada em 46 dos pacientes com psor&#237;ase&#44; enquanto nenhum sinal de artrite psori&#225;sica foi encontrado em 155 pacientes&#46; Quando os pacientes foram divididos em dois grupos de acordo com a idade de in&#237;cio da psor&#237;ase&#44; o n&#250;mero de pacientes com psor&#237;ase de in&#237;cio precoce &#40;idade &#8804; 40&#41; foi de 132&#44; e o n&#250;mero de pacientes com psor&#237;ase de in&#237;cio tardio &#40;idade<span class="elsevierStyleHsp" style=""></span>&#62; 40&#41; foi de 69&#46; Trinta e cinco dos pacientes tinham hist&#243;ria de psor&#237;ase em parentes de primeiro grau e em 166 pacientes n&#227;o foi identificada hist&#243;ria de psor&#237;ase em parentes de primeiro grau&#46; O n&#250;mero de pacientes cujo escore PASI &#40;do ingl&#234;s <span class="elsevierStyleItalic">Psoriasis Area and Severity Index</span>&#41; era &#8804; 10 foi 28&#44; e o restante do grupo de psor&#237;ase&#44; 173 pacientes&#44; apresentou escore PASI<span class="elsevierStyleHsp" style=""></span>&#62; 10&#46; As distribui&#231;&#245;es genot&#237;picas e as fra&#231;&#245;es al&#233;licas das popula&#231;&#245;es de estudo s&#227;o apresentadas na <a class="elsevierStyleCrossRef" href="#tbl0010">tabela 2</a>&#46; Tanto o grupo de pacientes quanto o grupo controle mostraram compatibilidade com o HWE&#46; H&#225; diferen&#231;a estatisticamente significante entre os grupos de pacientes e controle em termos de distribui&#231;&#245;es genot&#237;picas &#40;p &#60; 0&#44;001&#41;&#46; Os gen&#243;tipos TC e CC foram mais representados no grupo de pacientes do que no grupo controle &#40;24&#44;9&#37; <span class="elsevierStyleItalic">vs</span>&#46; 10&#44;2&#37;&#59; 2&#44;0&#37; <span class="elsevierStyleItalic">vs</span>&#46; 0&#44;2&#37;&#44; respectivamente&#41;&#46; Al&#233;m disso&#44; o alelo variante C foi mais prevalente no grupo de pacientes e isso foi estatisticamente significante &#40;p &#60; 0&#44;001&#41;&#44; e a presen&#231;a do alelo C foi associada a um risco 3&#44;14 vezes maior de psor&#237;ase &#40;IC95&#37; 2&#44;015&#8208;24&#44;921&#41;&#46; Quando as distribui&#231;&#245;es genot&#237;picas no grupo de pacientes foram avaliadas em termos de hist&#243;ria familiar&#44; artrite psori&#225;sica&#44; idade de in&#237;cio e g&#234;nero&#44; n&#227;o foi observada diferen&#231;a estat&#237;stica &#40;dados n&#227;o mostrados&#41;&#46; Os resultados da an&#225;lise de regress&#227;o log&#237;stica para comprovar a rela&#231;&#227;o entre psor&#237;ase e o alelo IL&#8208;17F C tamb&#233;m confirmaram que o alelo variante C aumenta o risco de psor&#237;ase &#40;p &#60; 0&#44;001&#59; IC95&#37; 2&#44;015&#8208;4&#44;491&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0010"></elsevierMultimedia></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Discuss&#227;o</span><p id="par0030" class="elsevierStylePara elsevierViewall">Existem seis membros da fam&#237;lia IL&#8208;17 &#40;IL17A&#8208;IL17F&#41;&#44; que desempenham papel cr&#237;tico na patog&#234;nese da psor&#237;ase&#46;<a class="elsevierStyleCrossRefs" href="#bib0270"><span class="elsevierStyleSup">20&#8211;22</span></a> Os mais estudados s&#227;o IL&#8208;17A e IL&#8208;17F&#44; que t&#234;m fun&#231;&#245;es biol&#243;gicas semelhantes&#44; mostrando 50&#37; de homologia&#46; Ambos t&#234;m sido frequentemente associados a muitas doen&#231;as inflamat&#243;rias&#44; incluindo a psor&#237;ase&#46;<a class="elsevierStyleCrossRefs" href="#bib0285"><span class="elsevierStyleSup">23&#8211;25</span></a> Embora a IL&#8208;17A pare&#231;a desempenhar papel central na patog&#234;nese da psor&#237;ase&#44; estudos recentes relataram um n&#237;vel crescente de IL&#8208;17F na pele lesionada da psor&#237;ase&#44; al&#233;m da demonstra&#231;&#227;o de que IL&#8208;17F tem fun&#231;&#245;es semelhantes &#224;s de IL&#8208;17A e come&#231;ou&#8208;se a focar no poss&#237;vel papel cr&#237;tico de IL&#8208;17F na imunopatog&#234;nese da doen&#231;a&#46;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">26</span></a> Os resultados de um estudo recente de Bertelsen et al&#46; forneceram evid&#234;ncias de que IL&#8208;17F desempenha papel fundamental no eixo IL&#8208;23&#47;IL&#8208;17<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">26</span></a> e mostraram que a estimula&#231;&#227;o de IL&#8208;17F induz a express&#227;o de I&#954;B&#954;&#44; cujo papel cr&#237;tico na patog&#234;nese da psor&#237;ase foi demonstrado anteriormente<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">27</span></a> em queratin&#243;citos humanos&#44; alterando os n&#237;veis de mRNA e de prote&#237;na&#44; e desempenhando papel na regula&#231;&#227;o de muitos genes&#44; como os associados &#224; psor&#237;ase&#46;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">26</span></a> Outras evid&#234;ncias acumuladas mostram que a variante IL&#8208;17F rs763780 produz diferentes respostas medicamentosas &#224;s abordagens terap&#234;uticas&#46; Essa situa&#231;&#227;o destacou mais uma vez o papel cr&#237;tico da IL&#8208;17F na patog&#234;nese da psor&#237;ase&#46;<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">28</span></a> Os pesquisadores avaliaram a resposta PASI 75 em um grupo de estudo de 194 pacientes com psor&#237;ase e associaram o gen&#243;tipo IL17F rs763780 TT a melhor resposta ao tratamento com ustequinumabe&#46; Dados de outro estudo no qual ustequinumabe foi administrado tamb&#233;m relataram diminui&#231;&#227;o nos n&#237;veis de IL&#8208;17A e IL&#8208;17F na semana 24&#44; mas essa diminui&#231;&#227;o foi significante apenas entre IL&#8208;17F e placebos&#46;<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">29</span></a> Embora o papel da IL&#8208;17F na imunopatog&#234;nese da psor&#237;ase n&#227;o tenha sido totalmente esclarecido&#44; a determina&#231;&#227;o das variantes desse gene &#233; de grande import&#226;ncia em termos de cria&#231;&#227;o de op&#231;&#245;es de tratamento paciente&#8208;espec&#237;ficas&#46; No entanto&#44; h&#225; poucos estudos sobre esse assunto na literatura&#44; e a investiga&#231;&#227;o &#233; bastante limitada&#46; Um desses estudos&#44; de Kaur et al&#46;&#44; associou a variante IL&#8208;17F rs763780 ao aumento da suscetibilidade &#224; psor&#237;ase&#46;<a class="elsevierStyleCrossRef" href="#bib0320"><span class="elsevierStyleSup">30</span></a> No presente estudo&#44; foi observado que os gen&#243;tipos portadores do alelo variante prevaleciam no grupo de pacientes em compara&#231;&#227;o ao grupo controle&#44; o que &#233; semelhante aos dados de Kaur et al&#46; Al&#233;m disso&#44; os autores avaliaram que o alelo variante est&#225; associado a um risco 3&#44;1 vezes maior de psor&#237;ase&#46; Da mesma maneira&#44; Choi et al&#46;&#44; que definiram IL&#8208;17F como um novo <span class="elsevierStyleItalic">locus</span> de risco para psor&#237;ase&#44; relataram que os gen&#243;tipos portadores do alelo variante estavam mais amplamente representados no grupo de pacientes&#46;<a class="elsevierStyleCrossRef" href="#bib0325"><span class="elsevierStyleSup">31</span></a> Consistente com esses dados&#44; outro estudo em popula&#231;&#227;o coreana relatou que o gen&#243;tipo da variante homozig&#243;tica estava associado a um risco 3&#44;27 vezes maior de psor&#237;ase&#46;<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">32</span></a> Contudo os dados de estudos conduzidos em popula&#231;&#245;es japonesas e espanholas<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">33</span></a> n&#227;o relataram associa&#231;&#227;o entre a variante IL&#8208;17F rs763780 e psor&#237;ase&#46; Isso pode ser explicado pelo fato de que um gene depende de seu contexto gen&#244;mico e pode exibir diferentes padr&#245;es de express&#227;o em diferentes grupos &#233;tnicos&#46;<a class="elsevierStyleCrossRef" href="#bib0340"><span class="elsevierStyleSup">34</span></a> Com base nas informa&#231;&#245;es obtidas do presente estudo&#44; os autores enfatizam a rela&#231;&#227;o da IL&#8208;17F com a psor&#237;ase&#46; Al&#233;m disso&#44; tem&#8208;se a impress&#227;o de que a variante IL&#8208;17F rs763780 induziu suscetibilidade &#224; doen&#231;a pelo alelo C&#46; Como a psor&#237;ase apresenta muitas comorbidades&#44; &#233; importante determinar os grupos de risco e aplicar precocemente as op&#231;&#245;es de tratamento&#46; A variante IL&#8208;17F rs763780 pode ser recomendada como biomarcador apropriado pois tratamentos apropriados&#44; visando o alvo correto&#44; possibilitar&#227;o aos m&#233;dicos diminuir a morbidade na doen&#231;a&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Limita&#231;&#245;es</span><p id="par0035" class="elsevierStylePara elsevierViewall">O presente estudo tem algumas limita&#231;&#245;es&#46; A primeira delas &#233; o tamanho relativamente pequeno da amostra&#46; Um tamanho de amostra maior aumentaria o poder estat&#237;stico&#46; A segunda limita&#231;&#227;o &#233; que n&#227;o foi poss&#237;vel medir os n&#237;veis de express&#227;o de IL&#8208;17F&#46; No entanto&#44; o presente estudo chama a aten&#231;&#227;o para a import&#226;ncia da IL&#8208;17F que merece ser avaliada em um grupo amostral maior&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Conclus&#227;o</span><p id="par0040" class="elsevierStylePara elsevierViewall">Com base nas informa&#231;&#245;es obtidas no presente estudo&#44; os autores enfatizam a rela&#231;&#227;o da IL&#8208;17F com a psor&#237;ase&#46; Al&#233;m disso&#44; os gen&#243;tipos IL&#8208;17F rs763780 TC e CC e o alelo C est&#227;o associados ao aumento do risco de psor&#237;ase na popula&#231;&#227;o turca&#44; de acordo com essa amostra&#46; Como a psor&#237;ase apresenta elevadas comorbidades&#44; &#233; importante determinar os grupos de risco e aplicar precocemente as op&#231;&#245;es de tratamento&#46; A variante IL&#8208;17F rs763780 pode ser recomendada como biomarcador apropriado pois tratamentos apropriados&#44; visando o alvo correto&#44; possibilitar&#227;o aos m&#233;dicos diminuir a morbidade na doen&#231;a&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Suporte financeiro</span><p id="par0045" class="elsevierStylePara elsevierViewall">O presente estudo foi financiado por uma bolsa da Scientific Research Projects Coordination Unit&#44; Giresun University &#40;Projeto n&#176; SA&#286;&#8208;BAP&#8208;A&#8208;270220&#8208;07&#41;&#46;</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Contribui&#231;&#227;o dos autores</span><p id="par0050" class="elsevierStylePara elsevierViewall">Ay&#351;eg&#252;l Ba&#351;ak Akadam&#8208;Teker&#58; Concep&#231;&#227;o do estudo&#44; fornecimento de amostras&#44; an&#225;lise dos dados&#44; pesquisa na literatura&#44; reda&#231;&#227;o do artigo e realiza&#231;&#227;o do trabalho laboratorial&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">Burak Ak&#351;an&#58; Fornecimento de amostras&#44; an&#225;lise dos dados e pesquisa na literatura&#46;</p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Conflito de interesses</span><p id="par0060" class="elsevierStylePara elsevierViewall">Nenhum&#46;</p></span></span>"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Fundamentos</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">A psor&#237;ase representa fen&#243;tipo inflamat&#243;rio cr&#244;nico moldado por intera&#231;&#245;es gen&#233;ticas&#44; caracterizado pela hiperprolifera&#231;&#227;o de queratin&#243;citos e comumente afetando a pele e as articula&#231;&#245;es&#46; Estudos experimentais e cl&#237;nicos sugerem que o <span class="elsevierStyleItalic">locus</span> do gene IL&#8208;17F desempenhe papel como citocina central na imunopatog&#234;nese da psor&#237;ase&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Objetivos</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Com base no papel central da IL&#8208;17F na patog&#234;nese da psor&#237;ase&#44; levantou&#8208;se a hip&#243;tese de que varia&#231;&#245;es nesse gene poderiam afetar a suscetibilidade e gravidade dessa doen&#231;a&#46; Portanto&#44; o presente estudo pretende analisar se a variante IL&#8208;17F rs763780 tem efeito na patog&#234;nese da psor&#237;ase na popula&#231;&#227;o turca&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">M&#233;todo</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Neste estudo de caso&#8208;controle&#44; o grupo de estudo consistiu em 603 pessoas &#40;201 pacientes com psor&#237;ase &#8211; 73 homens e 128 mulheres&#59; e 402 controles &#8211; 146 homens e 256 mulheres&#41; genotipados em termos do polimorfismo IL&#8208;17F rs763780 com o TaqMan 5&#8217; Allelic Discrimination Test&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Resultados</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">As distribui&#231;&#245;es genot&#237;picas do polimorfismo IL&#8208;17F rs763780 entre os grupos de pacientes e controle foram estatisticamente diferentes&#44; e os gen&#243;tipos TC &#40;gen&#243;tipo heterozigoto&#41; e CC &#40;gen&#243;tipo mutante homozigoto&#41; foram mais representados no grupo de pacientes do que no grupo controle &#40;24&#44;9&#37; <span class="elsevierStyleItalic">vs</span>&#46; 10&#44;2&#37;&#59; 2&#44;0&#37; <span class="elsevierStyleItalic">vs</span>&#46; 0&#44;2&#37;&#44; respectivamente&#41;&#46; Al&#233;m disso&#44; o alelo variante C foi mais prevalente no grupo de pacientes e isso foi estatisticamente significante &#40;p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41;&#44; e a presen&#231;a do alelo C foi associada a um risco 3&#44;14 vezes maior de psor&#237;ase &#40;IC 95&#37; 2&#44;015&#8208;24&#44;921&#41;&#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">O presente estudo tem algumas limita&#231;&#245;es&#46; A primeira delas &#233; o tamanho relativamente pequeno da amostra&#46; A segunda &#233; que n&#227;o foi poss&#237;vel medir os n&#237;veis da express&#227;o de IL&#8208;17F&#46; No entanto&#44; os dados do estudo chamam a aten&#231;&#227;o para a import&#226;ncia da IL&#8208;17F&#44; indicando que merece ser avaliada em um grupo amostral maior&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Conclus&#227;o</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Os autores relatam que o gen&#243;tipo IL&#8208;17F rs763780 TC e CC e o alelo C est&#227;o associados ao aumento do risco de psor&#237;ase na popula&#231;&#227;o turca&#46;</p></span>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Como citar este artigo&#58; Akadam&#8208;Teker AB&#44; Ak&#351;an B&#46; Association of IL&#8208;17F rs763780 polymorphism and risk of psoriasis in Turkish population&#58; a case&#8208;control study&#46; An Bras Dermatol&#46; 2024&#59;99&#58;357&#8211;61&#46;</p>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0010">Trabalho realizado no Departamento de Gen&#233;tica M&#233;dica e no Departamento de Doen&#231;as Cut&#226;neas&#44; Faculdade de Medicina&#44; Giresun University&#44; Giresun&#44; Turquia&#46;</p>"
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          "leyenda" => "<p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Os valores m&#233;dios foram comparados entre pacientes e controles por meio do teste <span class="elsevierStyleItalic">t</span> de Student&#46; Os dados qualitativos foram analisados pelo teste de Qui&#8208;Quadrado&#46;</p><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Os dados s&#227;o apresentados como m&#233;dia<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>DP e n &#40;&#37;&#41;&#46; Os valores em negrito foram estatisticamente significantes &#40;p &#60; 0&#44;05&#41;&#46;</p><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">NS&#44; n&#227;o significante&#44; PASI&#44; Psoriasis Area and Severity Index&#59; n&#44; n&#250;mero de amostras&#46;</p>"
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Controles&#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>402&#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&#8208;valor&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
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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\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">256 &#40;63&#44;7&#37;&#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
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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\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8208;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">155&#40;77&#44;5&#37;&#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
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">&#8208;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>HF&#8208;&nbsp;\t\t\t\t\t\t\n
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Article information
ISSN: 26662752
Original language: Portuguese
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