Association of Interferon Regulatory Factor-3 Gene Polymorphisms With Infection and Antiviral Efficacy of Chronic Hepatitis C Virus

Abstract

Background 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.Methods We retrospectively enrolled 178 patients with chronic hepatitis C (CHC) and 82 matched healthy controls between 2016 and 2019 at the Second Hospital of Wenzhou Medical University, China. All patients received a standard dose of polyethylene glycol interferon + ribavirin (PR regimen), and were divided into the response, non-response, sustained virological response (SVR), and non-sustained virological response (NSVR) groups based on their HCV RNA levels. 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.Results 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 (p<0.05). rs2304206 C>T but not rs2304204A>G was associated with increased risk for CHC (OR= 2.35 (95% CI: 1.30 to 4.24), p = 0.004), and reduced antiviral efficacy between both response groups (OR= 1.86 (95% CI: 1.06 to 3.24), p = 0.028) and SVR groups (OR= 1.79 (95% CI:1.05 to 3.06), p = 0.030). Haplotype GT type suffered negative consequence between the CHC and control groups, the responder and non-responder groups, and the SVR and non-SVR groups (p=0.004, 0.028, 0.030). The content of IFR-3 in CT genotype of rs2304206 was higher than that in CC genotype.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.