Department of Medicine, Division of Allergy, Immunology and Rheumatology, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taiwan, Republic of China.
Genes Immun. 2011 Jun;12(4):300-9. doi: 10.1038/gene.2011.1. Epub 2011 Feb 24.
Chronic hepatitis C virus (HCV) infection patients exhibit different sustained virological responses (SVRs) following the treatment with pegylated interferon-α (IFN-α) and ribavirin. Genome-wide association studies consistently linked SVR of IFN-α-based therapy to the IL28B single-nucleotide polymorphisms (SNPs) on chromosome 19q.13 in various populations. This study was undertaken to investigate the association of IL28B SNPs with SVR in a cohort of Taiwanese chronic HCV patients. Ten SNPs of IL28B were genotyped in 728 chronic HCV patients and 960 healthy controls. Genotype distributions, allele frequencies and haplotypes were tested for SVR and susceptibility in Taiwanese chronic HCV patients. Non-genotype 1 infection (adjusted P=3.3 × 10(-12), odds ratio (OR) 0.179; 95% confidence interval (CI): 0.110-0.290) and low HCV viral load (<400 000 IU ml(-1)) (adjusted P=3.5 × 10(-9), OR 0.299; 95% CI: 0.200-0.446) were two major factors identified for high SVR. Notably, eight IL28B SNPs including previously described disease-associated SNPs (Trend test P=0.005) were significantly associated with SVR. Our data indicate that IL28B polymorphisms are the essential contributing factors for high SVR in Taiwanese chronic HCV patients. Combination of virus genotyping and host genetic data may be used to select the optimal treatment regimes in IFN-based therapy.
慢性丙型肝炎病毒(HCV)感染患者在接受聚乙二醇干扰素-α(IFN-α)和利巴韦林治疗后表现出不同的持续病毒学应答(SVR)。全基因组关联研究一致将 IFN-α 治疗的 SVR 与染色体 19q.13 上的 IL28B 单核苷酸多态性(SNP)相关联。这项研究旨在调查 IL28B SNP 与台湾慢性 HCV 患者 SVR 的关联。在 728 例慢性 HCV 患者和 960 例健康对照者中,对 IL28B 的 10 个 SNP 进行了基因分型。对 IL28B 基因型分布、等位基因频率和单倍型进行了检测,以确定台湾慢性 HCV 患者的 SVR 和易感性。非基因型 1 感染(调整后的 P=3.3×10(-12),比值比(OR)0.179;95%置信区间(CI):0.110-0.290)和低 HCV 病毒载量(<400000 IU ml(-1))(调整后的 P=3.5×10(-9),OR 0.299;95% CI:0.200-0.446)是两个主要的高 SVR 因素。值得注意的是,包括以前描述的疾病相关 SNP 在内的 8 个 IL28B SNP(趋势检验 P=0.005)与 SVR 显著相关。我们的数据表明,IL28B 多态性是台湾慢性 HCV 患者高 SVR 的重要影响因素。病毒基因型和宿主遗传数据的结合可能用于选择 IFN 治疗中的最佳治疗方案。