Influência do polimorfismo genético de citocinas na hepatite C crônica em uma população do Rio de Janeiro

• Ano de defesa: 2013
• Autor(a) principal: Silva, Gustavo Milson Fabricio da
• Orientador(a): Pôrto, Luís Cristóvão de Moraes Sobrino
• Banca de defesa: Visentainer, Jeane Eliete Laguila , Paula, Vanessa Salete de , Perez, Renata de Mello , Silva, Dayse Aparecida da
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade do Estado do Rio de Janeiro
• Programa de Pós-Graduação: Programa de Pós-Graduação em Biologia Humana e Experimental
• Departamento: Centro Biomédico::Instituto de Biologia Roberto Alcantara Gomes
• País: BR
• Palavras-chave em Português: Hepatite C; Cirrose hepática; Vírus da hepatite; Polimorfismo (Genética); Citocinas; Polimorfismo de um único nucleotídeo; Hepatite C crônica; Vírus da hepatite C
• Palavras-chave em Inglês: Cytokines; Single nucleotide polymorphism; Chronic hepatitis C; Hepatitis C virus
• Área do conhecimento CNPq: CNPQ::CIENCIAS BIOLOGICAS::IMUNOLOGIA::IMUNOGENETICA
• Link de acesso: http://www.bdtd.uerj.br/handle/1/7778

Hepatitis C virus infection is one of the most common blood-borne infections worldwide. Approximately, 20% of infected patients successfully eliminate the virus, whereas the majority of patients develop chronic infection with a wide spectrum of liver lesions, ranging from a minimal inflammation to cirrhosis. The host's immune response is an important correlate of HCV infection outcome and disease progression. The aim of this study was to explore the possibility of the inheritance of cytokine gene polymorphisms as a candidate for susceptibility to persistent HCV infection or HCV clearance in a sample of Rio de Janeiro (Brazil) population. Genetic polymorphisms in the cytokines TNFA (-308), TGFB1 (codon 10 and 25), IL10 (-1082, -592), IL6 (-174) and IFNG (+874) were analyzed by polymerase chain reaction-sequence-specific primer (SSP) in 245 chronic hepatitis C (HCC) patients, 41 spontaneous recovery (SR) patients and 189 healthy volunteers. Further, IL28B (rs12979860, rs12980275 and rs8099917) were assessed by real-time PCR in all groups. Liver fibrosis and inflammation staging, response to treatment and virus genotype were also tested to influence in HCV chronic infection. IL28B rs12989760 CC and rs12980275 AA genotypes were significantly associated with spontaneous recovery of HCV infection and response to therapy. Likewise, C allele (rs12979860) and A allele (rs12980275) were also more frequent in SR group, while C allele of IL6 (-174) is associated with persistence to HCC. No association was found between other cytokine gene polymorphism and susceptibility to HCV infection and response to treatment. Multivariate analysis showed male, IL28B rs12979860 CT and TT and TGFB1 (codon 10) TC genotypes to be factors associated with HCC. TNFA (-308) GG genotype seems to be associated with moderate stage of inflammation. Also, ethnicity according self-declared is supposed to influence the distribution IL6 (-174) and IL28B rs12979860 and rs8099917 polymorphisms. These results suggest that the IL28B polymorphisms are associated with spontaneous clearance of HCV and response to therapy in a Brazilian population. Moreover, these results could be useful to further association between cytokine polymorphism and HCV infection outcome in Brazilian admixture population.