Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, No. 140 Hanzhong Road, Nanjing, 210029, Jiangsu, China.
Inflammation. 2015 Feb;38(1):142-51. doi: 10.1007/s10753-014-0016-x.
Hepatitis C virus (HCV) infection varies in the outcomes depending on both viral and host factors. This study aims to investigate the associations of three single nucleotide polymorphisms (SNPs) of Toll-like receptor 7 (TLR7), rs179016, rs5743733, and rs1634323, with susceptibility to HCV infection and clearance. The three SNPs were genotyped in a high-risk Chinese population, including 444 HCV spontaneous clearance cases, 732 persistent infection cases, and 1107 healthy controls. The G allele of rs1634323 was related to the protection from persistent infection among females (dominant model: odds ratio (OR) = 0.558, 95 % confidence interval (CI) = 0.348-0.894, P = 0.015). This protective effect was more evident in blood donation and HCV non-1 genotype-infected subgroups (all P < 0.05). The carriage of rs179016 C allele was more prone to develop persistent infection (OR = 1.444, 95 % CI = 1.096-1.903, P = 0.009) in males, and the risk effect remained significant among older (>50 years), hemodialysis (HD), and HCV-1 and HCV non-1 genotypes-infected subjects (all P < 0.05). Haplotype analyses showed that CCA haplotype among females was correlated with the elevated risk of HCV susceptibility while the carriage of GGA was more prone to be infected with HCV and CCA was more likely to develop persistent infection (all P < 0.05) among males. Our results first demonstrated that the carriage of rs179016 C allele had a negative effect on spontaneous clearance of HCV among males while rs1634323 G allele conferred a protective effect against persistent infection among female subjects.
丙型肝炎病毒 (HCV) 感染的结局因病毒和宿主因素的不同而有所不同。本研究旨在探讨 Toll 样受体 7 (TLR7) 的三个单核苷酸多态性 (SNP) rs179016、rs5743733 和 rs1634323 与 HCV 感染易感性和清除的相关性。在高危中国人群中对这三个 SNP 进行了基因分型,包括 444 例 HCV 自发性清除病例、732 例持续性感染病例和 1107 例健康对照。rs1634323 的 G 等位基因与女性持续性感染的保护作用有关(显性模型:比值比 (OR) = 0.558,95 %置信区间 (CI) = 0.348-0.894,P = 0.015)。这种保护作用在献血和 HCV 非 1 基因型感染亚组中更为明显(均 P < 0.05)。rs179016 C 等位基因的携带更容易导致持续性感染(OR = 1.444,95 % CI = 1.096-1.903,P = 0.009),在男性中,这种风险效应在年龄较大 (>50 岁)、血液透析 (HD) 和 HCV-1 和 HCV 非 1 基因型感染患者中仍然显著(均 P < 0.05)。单体型分析表明,女性的 CCA 单体型与 HCV 易感性升高相关,而 GGA 的携带更易感染 HCV,CCA 更易发展为持续性感染(均 P < 0.05)。我们的研究结果首次表明,rs179016 C 等位基因的携带对男性 HCV 的自发性清除有负面影响,而 rs1634323 G 等位基因对女性持续性感染有保护作用。