Hepatitis C virus (HCV) genotype 3 is very prevalent in Europe and Asia and is associated with worst outcomes than other genotypes. Genetic factors have been associated with HCV infection; however, no extensive genome-wide study has been performed among HCV genotype 3 patients. In this study, using a large cohort of 1,759 patients infected with HCV genotype 3, we explore the role of genetic variants on the response to interferon (IFN) and direct-acting antiviral (DAA) regimens and viremia in a combined candidate gene and genome-wide analysis. We show that genetic variants within the IFN lambda 4 (IFNL4) locus are the major factors associated with the studied traits, accordingly with observations in other HCV genotypes and with comparable effect sizes. In particular, the functional dinucleotide polymorphism rs368234815 was associated with IFN-based sustained virologic response (SVR) [odds ratio (OR) = 1.5, P = 2.3 × 10-7], viremia (beta = -0.23, P = 8.8 × 10-10), and also DAA-based SVR (OR = 1.7; P = 4.2 × 10-4). Our results provide evidence for a role of genetic variants on HCV viremia and SVR, notably DAA-based, in patients infected with HCV genotype 3.

中文翻译：

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IFNL4 遗传变异对丙型肝炎病毒基因 3 型患者持续病毒学反应和病毒血症的影响。

丙型肝炎病毒 (HCV) 基因型 3 在欧洲和亚洲非常普遍，与其他基因型相比，其结果最差。遗传因素与 HCV 感染有关；然而，尚未在 HCV 基因型 3 患者中进行广泛的全基因组研究。在这项研究中，我们使用由 1,759 名感染 HCV 基因型 3 的患者组成的大型队列，在候选基因和基因组组合中探讨遗传变异对干扰素 (IFN) 和直接作用抗病毒 (DAA) 方案和病毒血症的反应的作用- 广泛的分析。我们显示 IFN λ 4 (IFNL4) 基因座内的遗传变异是与所研究性状相关的主要因素，因此与其他 HCV 基因型的观察结果具有可比的效应大小。尤其是，功能性二核苷酸多态性 rs368234815 与基于 IFN 的持续病毒学应答 (SVR) [优势比 (OR) = 1.5, P = 2.3 × 10-7]、病毒血症 (beta = -0.23, P = 8.8 × 10-10) 相关，以及基于 DAA 的 SVR（OR = 1.7；P = 4.2 × 10-4）。我们的研究结果提供了基因变异对 HCV 病毒血症和 SVR 的作用的证据，特别是基于 DAA 的，在感染 HCV 基因型 3 的患者中。