Th17 细胞相关 RORC 基因的多态性与中国女性 HCV 的自发清除有关。

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

机构信息

Department of Microbiology and Center of Infectious Diseases, School of Basic Medical Sciences, Peking University, Beijing, 100191, China.

State Key laboratory of Infectious Disease Prevention and Control, National Center for AIDS/STD Control and Prevention, China CDC, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Beijing, China.

出版信息

BMC Infect Dis. 2018 Jun 4;18(1):254. doi: 10.1186/s12879-018-3153-2.

DOI:10.1186/s12879-018-3153-2

PMID:29866105

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5987631/

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.

摘要

背景

女性性别和有利的 IFNL3 基因型是 HCV 感染自发清除的主要独立预测因素。然而，许多携带有利 IFNL3 基因型的女性仍会发生慢性丙型肝炎感染，这表明其他宿主和/或病毒因素对感染的预后有影响。

方法

本研究纳入了 137 名抗 HCV 阳性的汉族女性慢性 HCV 携带者和 HCV 自发清除者。在 23 个基因中，选择了编码 HCV 共受体、转录因子、Toll 样受体、共刺激分子和细胞因子的 111 个 SNP 进行 SNP 分析。

结果

在对 23 个基因中的 111 个 SNP 的基因型和等位基因频率进行比较后，发现 RORC 基因中的 rs9826（CC/TT/CT 时 P=0.024；C 等位基因/T 等位基因时 P=0.015）和 rs1521177（GG/TT/GT 时 P=0.017；G 等位基因/T 等位基因时 P=0.006）与 HCV 自发性清除显著相关。在携带有利 IFNL3 基因型（rs12979860CC、rs8099917TT、rs12980275AA）的亚组中，rs1521177（基因型：P=0.040；等位基因：P=0.021）与 HCV 自发性清除仍显著相关。重要的是，rs9826-T/rs1521177-T 这一最常见的 RORC 单倍型在两个主要队列（P=0.0027 和 P=0.0117）和 IFNL3 有利亚组中，在清除者和携带者中的出现频率有显著差异。