Clearance of acute infection with hepatitis C virus (HCV) is associated with the chr19q13.13 region containing the rs368234815 (TT/ΔG) polymorphism. We fine-mapped this region to detect possible causal variants that may contribute to HCV clearance. First, we performed sequencing of IFNL1-IFNL4 region in 64 individuals sampled according to rs368234815 genotype: TT/clearance (N = 16) and ΔG/persistent (N = 15) (genotype-outcome concordant) or TT/persistent (N = 19) and ΔG/clearance (N = 14) (discordant). 25 SNPs had a difference in counts of alternative allele >5 between clearance and persistence individuals. Then, we evaluated those markers in an association analysis of HCV clearance conditioning on rs368234815 in two groups of European (692 clearance/1 025 persistence) and African ancestry (320 clearance/1 515 persistence) individuals. 10/25 variants were associated (P < 0.05) in the conditioned analysis leaded by rs4803221 (P value = 4.9 × 10⁻⁰⁴) and rs8099917 (P value = 5.5 × 10⁻⁰⁴). In the European ancestry group, individuals with the haplotype rs368234815ΔG/rs4803221C were 1.7× more likely to clear than those with the rs368234815ΔG/rs4803221G haplotype (P value = 3.6 × 10⁻⁰⁵). For another nearby SNP, the haplotype of rs368234815ΔG/rs8099917T was associated with HCV clearance compared to rs368234815ΔG/rs8099917G (OR: 1.6, P value = 1.8 × 10⁻⁰⁴). We identified four possible causal variants: rs368234815, rs12982533, rs10612351 and rs4803221. Our results suggest a main signal of association represented by rs368234815, with contributions from rs4803221, and/or nearby SNPs including rs8099917.

丙型肝炎病毒 (HCV) 急性感染的清除与含有 rs368234815 (TT/ΔG) 多态性的 chr19q13.13 区域相关。我们对该区域进行了精细绘制，以检测可能有助于 HCV 清除的可能因果变异。首先，我们根据 rs368234815 基因型对 64 名个体进行了IFNL1-IFNL4区域测序：TT/清除 ( N = 16) 和 ΔG/持续 ( N = 15)（基因型-结果一致）或 TT/持续 ( N = 19) ）和 ΔG/间隙（ N = 14）（不一致）。清除个体和持久个体之间的 25 个 SNP 在替代等位基因 >5 的计数上存在差异。然后，我们在两组欧洲（692 清除率/1 025 持久性）和非洲血统（320 清除率/1 515 持久性）个体中对 rs368234815 的 HCV 清除条件进行关联分析，评估了这些标记。在 rs4803221（ P值 = 4.9 × 10 ^-04 ）和 rs8099917（ P值 = 5.5 × 10 ^-04 ）主导的条件分析中，10/25 变异相关（ P < 0.05）。在欧洲血统组中，具有单倍型 rs368234815ΔG/rs4803221C 的个体比具有 rs368234815ΔG/rs4803221G 单倍型的个体清除的可能性高 1.7 倍（ P值 = 3.6 × 10 ^-05 ）。对于另一个附近的SNP，与rs368234815ΔG/rs8099917G相比，rs368234815ΔG/rs8099917T的单倍型与HCV清除相关（OR：1.6， P值=1.8×10 ^-04 ）。我们确定了四种可能的致病变异：rs368234815、rs12982533、rs10612351 和 rs4803221。 我们的结果表明，主要的关联信号以 rs368234815 为代表，并有 rs4803221 和/或附近的 SNP（包括 rs8099917）的贡献。