Impact of KIR3DL1/3DS1 and HLA-B polymorphisms on hepatitis C virus infection: a case-control study

The polymorphism of killer-cell immunoglobulin-like receptors (KIRs) and human leukocyte antigen (HLA) genes determines the host's susceptibility to viral infections. This study aimed to investigate the impact of five single nucleotide polymorphisms (SNPs) in KIR3DL1/3DS1 and HLA-B genes on hepatitis C virus (HCV) infection. A total of 1881 individuals participated in this case-control study. SNPs including KIR3DL1/3DS1 rs613491, rs605219, rs620977 and HLA-B rs3819288, rs1131170 were genotyped. Using multivariable logistic regression adjusting for established genetic and demographic confounders combined with stratified analysis and multidimensional bioinformatics analysis was employed to analyze the association between SNPs and HCV infection. Logistic regression analysis revealed that KIR3DL1/3DS1 rs613491 CC and HLA-B rs1131170 CC were associated with increased susceptibility to HCV (codominant model: OR = 3.13, 95% CI = 1.90-5.17, P < 0.001; and OR = 4.20, 95% CI = 2.79-6.33, P < 0.001, respectively), whereas HLA-B rs1131170 AC showed a reduced susceptibility to HCV (codominant model: OR = 0.63, 95% CI = 0.49-0.81, P < 0.001). We speculate that the protective rs1131170-AC genotype may enhance either the quantity or quality of HCV-antigen presentation, thereby reducing susceptibility to infection. Stratified analysis indicated that rs613491 and rs1131170 also increased HCV susceptibility in certain subgroups. Bioinformatics analysis suggested the regulatory potential of these SNPs and their role in altering messenger RNA secondary structure, suggesting potential functional relevance that requires experimental validation in HCV susceptibility. Our findings demonstrate that KIR3DL1/3DS1 rs613491 CC and HLA-B rs1131170 CC are significantly associated with increased HCV susceptibility, while rs1131170 AC is associated with reduced susceptibility.