Association of Interferon Regulatory Factor-3 gene polymor- phisms with infection and antiviral efficacy of chronic hepatitis C virus

Abstract

Hepatitis C virus (HCV) is a major public health concern in developing countries. Pathogenesis of hepatitis C infection is poorly understood. Previously, we found higher Interferon Regulatory Factor-3 (IRF-3) expression in HCV-infected patients. However, the effect of IRF-3 polymorphism on the incidence of HCV infection and antiviral efficacy has not been sufficiently evaluated. In this retrospectively study, 178 patients with chronic hepatitis C (CHC) and 82 matched healthy controls were enrolled. All patients received standard dose of polyethylene glycol interferon and ribavirin (PR regimen), and were assigned to response, non-response, sustained virological re-sponse (SVR), and non-sustained virological response (NSVR) groups based on their content of HCV RNA. Gene polymorphisms were detected by DNA sequencing, and the plasma IRF-3 and IFN-β levels were measured by ELISA to assess the impact of IRF-3 gene variations and contents on the risk of HCV infection and antiviral efficacy. The results showed that plasma contents of IRF-3 and IFN-β were significantly different between the CHC and control groups, the response and non-response groups, and the SVR and non-SVR groups. rs2304206 C > T but not rs2304204A > G was associated with increased risk for CHC, and reduced antiviral efficacy between both response groups and SVR groups. Haplotype GT type suffered negative consequence be-tween the CHC and control groups, the responder and non-responder groups, and the SVR and non-SVR groups. The content of IFR-3 in CT genotype of rs2304206 was higher than that in CC genotype. In conclusion, the polymorphism of IFR-3 affects the plasma levels of IFR-3 and associated with HCV infection and interferon antiviral efficacy, where the T allele of rs2304206 may be a susceptibility factor for CHC and adversely impact interferon antiviral response.