Institute of Liver Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Viral Immunol. 2010 Jun;23(3):251-7. doi: 10.1089/vim.2009.0102.
Genetic polymorphism of IFNAR-1 plays a large role in determining the clearance or chronicity after hepatitis B virus (HBV) exposure. However, it is not clear whether type I interferon receptor-1 (IFNAR-1) variations continuously exert their effects to influence the final outcomes following HBV chronicity, including acute-on-chronic hepatitis B liver failure (ACLF-HBV), chronic hepatitis B (CHB), liver cirrhosis (LC), and hepatocellular carcinoma (HCC). Here we report that these four potential outcomes of chronic HBV infection are strongly associated with IFNAR-1 polymorphisms through a hospital-based case-control study of 663 cases. ACLF-HBV and HCC were each compared with CHB+LC. In comparison with the G/G genotype, the C/G and C/C genotypes at both single-nucleotide polymorphism (SNP) sites (rs1012335 and rs2257167) showed significant susceptibility to ACLF-HBV (the highest odds ratio [OR] reached 2.374; 95% CI = 1.488, 3.788; p < 0.001 for the C/G genotype at rs2257167), as well as HCC (OR = 2.475; 95% CI = 1.435, 4.426; p < 0.001 for the C/C genotype at rs1012335). The C allele at both loci was a susceptibility allele for ACLF-HBV and HCC, with the highest ORs reaching 1.653 (95% CI = 1.233, 2.216; p < 0.01 at rs1012335) in the ACLF-HBV group, and 1.659 (95% CI = 1.274, 2.159; p < 0.01 at rs1012335) in the HCC group. A strongly linked disequilibrium was also found within these two alleles (p < 0.001). Our research indicates that genetic polymorphisms of IFNAR-1 not only contribute to the determination of clearance or chronicity in the early stages of HBV exposure, but they also persistently influence pathogenesis over the long-term process of chronic HBV infection.
干扰素受体 1 的遗传多态性在乙型肝炎病毒（HBV）暴露后清除或慢性化中起着重要作用。然而，目前尚不清楚 I 型干扰素受体 1（IFNAR-1）的变异是否会持续发挥作用，从而影响 HBV 慢性感染的最终结局，包括乙型肝炎慢加急性肝衰竭（ACLF-HBV）、慢性乙型肝炎（CHB）、肝硬化（LC）和肝细胞癌（HCC）。本研究通过对 663 例病例的医院为基础的病例对照研究，报告称这四种慢性 HBV 感染的潜在结局与 IFNAR-1 多态性密切相关。ACLF-HBV 和 HCC 分别与 CHB+LC 进行比较。与 G/G 基因型相比，两个单核苷酸多态性（SNP）位点（rs1012335 和 rs2257167）的 C/G 和 C/C 基因型均显著易患 ACLF-HBV（rs2257167 处 C/G 基因型的最高比值比[OR]达到 2.374；95%CI=1.488，3.788；p<0.001），以及 HCC（rs1012335 处 C/C 基因型的 OR=2.475；95%CI=1.435，4.426；p<0.001）。两个位点的 C 等位基因均为 ACLF-HBV 和 HCC 的易感等位基因，在 ACLF-HBV 组中最高 OR 达到 1.653（95%CI=1.233，2.216；p<0.01），在 HCC 组中最高 OR 达到 1.659（95%CI=1.274，2.159；p<0.01）。在这两个等位基因中也发现了强烈的连锁不平衡（p<0.001）。我们的研究表明，IFNAR-1 的遗传多态性不仅有助于在 HBV 暴露的早期阶段确定清除或慢性化，而且还会在慢性 HBV 感染的长期过程中持续影响发病机制。
