Objective To explore correlations of single nucleotide polymorphism (SNP) at KIR3DL1 rs35974949 and rs35656676 with the susceptibility and chronicity of hepatitis C virus (HCV) infection and to provide clinical evidences for screening, diagnosis and individualized prevention of HCV infection.
Methods With cluster sampling from August 2008 to December 2015, we conducted face-to-face questionnaire interview, detections of HCV RNA, anti-HCV antibodies and other related serum indicators, and genotyping of KIR3DL1 r35974949 and rs35656676 with quantitative real-time PCR TaqMan assay among 2 537 people aged 18 – 79 years and at high risk of HCV infection but not ever having interferon and direct antiviral drug treatment, including 1 788 rural residents with paid blood donation history from 25 villages and 749 hemodialysis patients from 9 tertiary hospitals in Jiangsu province. According to detection results, the participants were then assigned into one of the three groups: uninfected control group (1 512 individuals) being seronegative for both anti-HCV antibodies and HCV RNA, spontaneous HCV clearance group (382) being seropositive for anti-HCV antibodies but seronegative for HCV RNA, and persistent HCV infection group (643) being seropositive for both anti-HCV antibodies and HCV RNA. Multivariate logistic regression models were used to analyze relationships between SNP at KIR3DL1 rs35974949 and rs35656676 and the susceptibility and chronicity of HCV infection.
Results The proportions of KIR3DL1 rs35974949 GG, GT and TT genotype carriers were 78.47%, 20.05% and 1.49% in control group; 76.64%, 19.16% and 4.20% in spontaneous clearance group; and 74.34%, 19.60% and 6.07% in persistent HCV infection group; while, those of KIR3DL1 rs35656676 CC, CG and GG genotype carriers were 31.32%, 50.60% and 18.08% in control group; 31.68%, 49.74% and 18.59% in spontaneous clearance group; and 31.78%, 50.47% and 17.76% in persistent HCV infection group, respectively. After adjusting for gender, age, alanine aminotransferase (ALT) abnormality, aspartate aminotransferase (AST) abnormality and route of HCV infection, unconditional multivariate logistic regression analysis demonstrated that the individuals carrying KIR3DL1 rs35974949 TT genotype were more likely to have an increased HCV susceptibility (codominant model: adjusted odds ratio aOR = 2.802, 95% confidence interval 95% CI: 1.571 – 4.998, P < 0.001; recessive genetic model: aOR = 2.860, 95% CI: 1.607 – 5.090, P < 0.001) compared with those carrying KIR3DL1 rs35974949 GG/GT genotype. However, no significant association of KIR3DL1 rs35974949 genotype with HCV chronicity was derived. Furthermore, no significant associations of KIR3DL1 rs35656676 polymorphism with HCV susceptibility and chronicity were observed.
Conclusion Single nucleotide polymorphism at KIR3DL1 rs35974949 is associated with increased susceptibility of HCV infection in high risk populations.
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