Polymorphisms in the Th17 cell-related RORC gene are associated with spontaneous clearance of HCV in Chinese women

Abstract

Background: Female gender and favorable IFNL3 genotypes are the primary independent predictors of spontaneous clearance of HCV infection. However, chronic hepatitis C infection occurs in numerous women carrying favorable IFNL3 genotypes, indicating that other host and/or virological factors contribute to the prognosis of infection.

Methods: A cohort of 137 anti-HCV-positive female Han Chinese cases, including 64 chronic HCV carriers and 73 HCV spontaneous resolvers, was recruited in the study. 111 SNPs in 23 genes encoding HCV co-receptors, transcription factors, Toll-like receptors, co-stimulating molecules, and cytokines were selected for SNP analysis.

Results: After comparison of genotypes and allelotype frequencies of 111 SNPs in 23 genes in the primary cohort, the SNPs rs9826 (P = 0.024 for CC/TT/CT; P = 0.015 for C allele/T allele) and rs1521177 (P = 0.017 for GG/TT/GT; P = 0.006 for G allele/T allele) in the RORC gene were significantly associated with spontaneous HCV clearance. In the sub-cohort carrying favorable IFNL3 genotypes (rs12979860CC, rs8099917 TT, rs12980275 AA), rs1521177 (genotype: P = 0.040; allelotype: P = 0.021) remained significantly associated with spontaneous HCV clearance. Importantly, the most common RORC haplotype rs9826-T/rs1521177-T was presented at significantly different frequencies in resolvers and carriers in both the primary cohort (P = 0.0027) and the IFNL3 favorable sub-cohort (P = 0.0117).

Conclusions: This study indicates that genetic polymorphisms in human Th17-related RORC gene are associated with different natural prognosis of HCV infection. The RORC haplotype, rs9826-T/rs1521177-T, was favorable for spontaneous clearance of HCV infection.

Keywords: HCV; IFNL3; Polymorphism; RORC; Spontaneous clearance.

Fig. 1

Flow diagram of study cohort selection. From a total of 1252 residents of Wangying Village, Shangcai County, 190 anti-HCV-positive female Chinese Han individuals were initially recruited to the study after screening. Of these 190 subjects, 53 HIV-positive women with chronic HCV infections were excluded. The remaining 137 females constituted the primary cohort, which consisted of “Chronic” (HIV- HCV carriers, n = 64) and “Resolved” (total n = 73: HIV+ HCV resolvers, n = 28, and HIV- HCV resolvers, n = 45) groups. An IFNL3 favorable sub-cohort was also constructed by exclusion of women with unfavorable IFNL3 genotypes (rs12979860 TC/TT, rs80999917 TG/TT, and rs12980275AG/GG; “Chronic”, n = 54, and “Resolved”, n = 67)