Association of cytokine gene polymorphisms with hepatitis C virus infection in a population from Rio de Janeiro, Brazil.

ABSTRACT

BACKGROUND: The host immune response is an important indicator of the outcome of hepatitis C virus (HCV) infection and disease progression. The aim of this study was to explore cytokine gene polymorphisms as a candidate for susceptibility to persistent HCV infection or HCV spontaneous clearance in a population from Rio de Janeiro, Brazil. METHODS: Genetic polymorphisms in the cytokines, tumor necrosis factor-alpha (-308), transforming growth factor-beta 1 (codons 10 and 25), interleukin-10 (IL-10; -1082 and -592), IL-6 (-174), and interferon-gamma (+874) were analyzed by polymerase chain reaction sequence-specific primers in 245 patients with chronic hepatitis C (CHC), 41 spontaneous recovery (SR) patients, and 189 healthy volunteers. Further, polymorphisms in IL-28B (rs12979860, rs12980275, and rs8099917) were assessed by real-time polymerase chain reaction in all groups. RESULTS: The IL-28B rs12979860 CC and rs12980275 AA genotypes were significantly associated with SR of HCV infection and response to therapy, whereas the C allele of IL-6 (-174) was associated with protection to CHC. A multivariate analysis showed that the male sex and IL-28B rs12979860 CT and TT and transforming growth factor-beta 1 (codon 10) TC genotypes were factors associated with CHC. Additionally, IL-6 (-174) C allele was increased in SR patients compared with patients with CHC. CONCLUSION: IL-28B polymorphisms are associated with spontaneous clearance of HCV and response to therapy in a Brazilian population. Also, IL-6 (-174) C allele is involved in SR and decreased inflammation scores.