Objective  To explore effects of single nucleotide polymorphism (SNP) in KIR2DL4 rs649216 and its ligand HLA-G rs1063320 on hepatitis C virus (HCV) infection susceptibility and chronicity and to provide evidence for screening, diagnosis and prevention of HCV infection.

  Methods  Totally 1 854 high-risk adults (18 – 80 years old) of HCV infection without the history of anti-HCV therapy (interferon or antiviral drugs treatment) were recruited with cluster sampling in two compulsory drug rehabilitation centers and hemodialysis rooms of 9 hospitals in two cities of Jiangsu province from October 2011 to December 2015; all the participants (1 121 drug addicts and 733 hemodialysis patients) were assigned into three groups according to the results of two separate HCV antibody and HCV RNA detections during previous 6 months before the survey: 1 341 in an uninfected group (negative for both HCV antibody and HCV RNA), 301 in a spontaneous HCV clearance group (positive for HCV antibody but negative for HCV RNA), and 202 in a persistent HCV infection group (positive for both HCV antibody and HCV RNA). Face-to-face questionnaire interview was conducted among the participants and fasting venous blood samples of the participants were collected for detections of HCV antibody, HCV RNA, HCV genotype, and genotype of targeted genes with TaqMan probe-based real-time quantitative PCR. Multivariate logistic regression model was adopted in analyses on the associations of SNP in KIR2DL4 rs649216 and its ligand HLA-G rs1063320 locus with HCV susceptibility and chronicity.

  Results  The proportions for carriers of genotype CC, CT and TT of KIR2DL4 rs649216 were 69.15%, 28.15% and 2.69% in the uninfected group; 73.90%, 23.05% and 3.05% in the spontaneous clearance group; and 62.25%, 33.82% and 3.92% in the persistent infection group; while, those for carriers of genotype GG, GC and CC of HLA-G rs1063320 were 32.89%, 51.25% and15.86% in the uninfected group; 34.29%, 45.36% and 20.36% in the spontaneous clearance group; and 33.15%, 47.28% and 19.57% in the persistent infection group, respectively. After adjusting for gender, age, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and infection route, unconditional multivariate logistic regression analyses showed that compared with the those with the genotype CC of KIR2DL4 rs649216, the participants with the genotype CT/TT of KIR2DL4 rs649216 were at a higher risk of chronic HCV infection (co-dominant model: odds ratio OR = 1.682, 95 % confidence interval 95% CI: 1.109 – 2.551; dominant model: OR = 1.671, 95% CI: 1.121 – 2.493); the participants carrying allele T of KIR2DL4 rs649216 were at an increased risk of chronic HCV infection (additive model: OR = 1.508, 95% CI: 1.070 – 2.125) in comparison with those carrying allele C of KIR2DL4 rs649216; moreover, in comparison with those carrying genotype GG + GC of HLA-G rs1063320, the participants carrying genotype CC of HLA-G rs1063320 were more likely to have HCV infection (recessive model: OR = 1.361, 95% CI: 1.018 – 1.819).

  Conclusion  The SNP of KIR2DL4 rs649216 is associated with the chronicity of HCV infection and the SNP of KIR2DL4’s ligand HLA-G rs1063320 is associated with the susceptibility to HCV infection.