Genetic variation in IL28RA is associated with the outcomes of HCV infection in a high-risk Chinese population

Abstract

Hepatitis C virus (HCV) infection varies in the outcomes depending on both viral and host factors. This study aims to investigate the association of single-nucleotide polymorphisms (SNPs) of IFNAR2, IL10RB, and IL28RA genes with susceptibility to HCV infection and resolution. Genotyping of IFNAR2, IL10RB, and IL28RA gene polymorphisms were performed using TaqMan® method from 552 patients with sero-positive anti-HCV and 421 uninfected controls. The distribution of IFNAR2 and IL10RB genotypes among the control, persistent infection, and spontaneous clearance groups did not differ. However, IL28RA-rs10903035 A allele was over-represented in persistent infection group when compared with uninfected controls and spontaneous clearance group, respectively (OR=1.54, 95%CI=1.23-1.92, P=0.004; OR=1.42, 95%CI=1.12-1.81, P=0.016), and AA genotype had a significant increased risk of persistent infection in different strata except for the females subgroup (P<0.05). IL28RA-rs11249006 GG genotype showed reduced susceptibility to persistent HCV infection (OR=0.53, 95%CI=0.31-0.91, P=0.044), and the protective effect was significantly different among subgroups stratified by age and likely source of infection (P<0.05). Besides, AG genotype had a significant negative effect on spontaneous clearance of HCV among young subjects (aged ⩽40) and patients infected with viral genotype-1 (P<0.05). Stratified analysis also showed that IL10RB-rs2834167 AG genotype was associated with an increased risk of persistent HCV infection in females, and GG genotype was associated with an increased risk of persistent HCV infection in females and patients with viral genotype non-1 (P<0.05). Haplotype analysis showed that IL28RA rs10903035-rs11249006 haplotype GG played a protective effect for HCV infection (OR=0.21, 95%CI=0.13-0.36, P<0.001; OR=0.20, 95%CI=0.12-0.34, P<0.001). This study indicates that two SNPs in IL28RA are correlated with susceptibility to HCV infection and spontaneous viral clearance, which implicates a primary role of IL28RA in the outcomes of HCV infection.