Knapp Susanne, Hennig Branwen J W, Frodsham Angela J, Zhang Lyna, Hellier Simon, Wright Mark, Goldin Rob, Hill Adrian V S, Thomas Howard C, Thursz Mark R
Faculty of Medicine, Imperial College, St Mary's Hospital Campus, Norfolk Place, W2 1NY, London, UK.
Immunogenetics. 2003 Sep;55(6):362-9. doi: 10.1007/s00251-003-0594-5. Epub 2003 Aug 26.
The natural outcome and response to treatment in hepatitis C virus (HCV) infection varies between individuals. Whereas some variation may be attributable to viral and environmental variables, it is probable that host genetic background also plays a significant role. Interleukin (IL)-10 has a key function in the regulation of cellular immune responses and in the suppression of pro-inflammatory cytokine secretion. Functional polymorphisms in the IL-10 gene have been described. We investigated the role of these polymorphisms in the outcome of HCV infection, treatment response and development of fibrosis in a case-control association study. Self-limiting infection was associated with the IL-10 (-592) AA genotype (OR=2.05; P=0.028). Persistent infection was associated with the IL-10 (-1082) GG genotype (OR=0.48; P=0.018). Sustained response to interferon therapy was associated with the IL-10 (-1082) GG genotype (OR=2.28; P=0.005) and the haplotype GCC (OR=2.27; P=0.020). The IL-10 (-1082) AA genotype and the ATA/ATA and ACC/ACC homozygous haplotypes were more frequent among patients with rapid fibrosis. Furthermore, the microsatellites IL-10.R and IL-10.G were associated with interferon response with IL-10R.2 conveying susceptibility (OR=1.80; P=0.034), and IL-10R.3 and IL-10.G13 being protective (OR=0.47; P=0.003 and OR=0.59; P=0.042, respectively). We conclude that polymorphisms in the IL-10 promoter appear to have some influence on the outcome of HCV infection, treatment and development of fibrosis.
丙型肝炎病毒（HCV）感染的自然转归以及对治疗的反应在个体间存在差异。虽然部分差异可能归因于病毒和环境变量，但宿主遗传背景可能也起着重要作用。白细胞介素（IL）-10在细胞免疫反应调节及促炎细胞因子分泌抑制中起关键作用。已报道了IL-10基因的功能性多态性。我们在一项病例对照关联研究中调查了这些多态性在HCV感染转归、治疗反应及纤维化发展中的作用。自限性感染与IL-10（-592）AA基因型相关（比值比[OR]=2.05；P=0.028）。持续性感染与IL-10（-1082）GG基因型相关（OR=0.48；P=0.018）。对干扰素治疗的持续反应与IL-10（-1082）GG基因型相关（OR=2.28；P=0.005）以及单倍型GCC相关（OR=2.27；P=0.020）。IL-10（-1082）AA基因型以及ATA/ATA和ACC/ACC纯合单倍型在纤维化进展迅速的患者中更为常见。此外，微卫星IL-10.R和IL-10.G与干扰素反应相关，其中IL-10R.2具有易感性（OR=1.80；P=0.034），而IL-10R.3和IL-10.G13具有保护作用（分别为OR=0.47；P=0.003和OR=0.59；P=0.042）。我们得出结论，IL-10启动子多态性似乎对HCV感染转归、治疗及纤维化发展有一定影响。
