Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, PR China.
Infect Genet Evol. 2011 Oct;11(7):1682-9. doi: 10.1016/j.meegid.2011.06.016. Epub 2011 Jun 30.
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.
丙型肝炎病毒（HCV）感染的结局因病毒和宿主因素而异。本研究旨在探讨干扰素受体 2（IFNAR2）、白细胞介素 10 受体β（IL10RB）和白细胞介素 28A（IL28RA）基因单核苷酸多态性（SNPs）与 HCV 感染易感性和清除的关系。采用 TaqMan®法对 552 例抗 HCV 血清阳性患者和 421 例未感染对照者的 IFNAR2、IL10RB 和 IL28RA 基因多态性进行基因分型。在对照组、持续性感染组和自发性清除组中，IFNAR2 和 IL10RB 基因型的分布无差异。然而，与未感染对照组和自发性清除组相比，IL28RA-rs10903035 A 等位基因在持续性感染组中过度表达（OR=1.54，95%CI=1.23-1.92，P=0.004；OR=1.42，95%CI=1.12-1.81，P=0.016），除女性亚组外（P<0.05），AA 基因型显著增加持续性感染的风险。IL28RA-rs11249006 GG 基因型对持续性 HCV 感染的易感性降低（OR=0.53，95%CI=0.31-0.91，P=0.044），且其保护作用在年龄和可能的感染来源分层亚组中差异有统计学意义（P<0.05）。此外，AG 基因型对年轻（≤40 岁）和感染病毒基因型 1 的患者的 HCV 自发性清除有显著的负面影响（P<0.05）。分层分析还显示，IL10RB-rs2834167 AG 基因型与女性持续性 HCV 感染风险增加相关，GG 基因型与女性和非 1 型病毒基因型患者持续性 HCV 感染风险增加相关（P<0.05）。单体型分析显示，IL28RA rs10903035-rs11249006 单体型 GG 对 HCV 感染有保护作用（OR=0.21，95%CI=0.13-0.36，P<0.001；OR=0.20，95%CI=0.12-0.34，P<0.001）。本研究表明，IL28RA 中的两个 SNP 与 HCV 感染易感性和自发性病毒清除相关，这表明 IL28RA 在 HCV 感染结局中起主要作用。
