Genetic mutations in NF-κB pathway genes were associated with the protection from hepatitis C virus infection among Chinese Han population

Host genetic polymorphism is one of major unalterable major factors for HCV infection. NF-κB proteins play multiple roles in immune response and involve in HCV infection and progression. This study was conducted to explore the relationship between single nucleotide polymorphisms (SNPs) in NF-κB pathway and the susceptibility as well as resolution of HCV infection. A total of 1642 Chinese subjects were enrolled in the study, including 963 uninfected control cases, 231 cases with spontaneous viral clearance and 448 cases with persistent HCV infection, and four SNPs (Rel rs842647, NF-κB2 rs12769316, RelA rs7101916, RelB rs28372683) were genotyped by TaqMan assay among them. Potentially functional polymorphisms were analyzed using online bioinformatics tools. The logistic analyses results indicated that RelA rs7101916 T allele (P(Bonferroni) = 0.016) and RelB rs28372683 A allele (P(Bonferroni) = 4.8e-5) were associated with an decreased risk of the susceptibility to HCV infection among Chinese Han population, which were consistent with the results of cumulative effects and haplotype analysis. The silico analysis of SNPs function suggested that the genetic variation of rs7101916 and rs28372683 could influence gene transcriptional regulation and expression, subsequently affecting NF-κB pathway activation and the susceptibility to HCV infection. This study firstly reported that the carriage of RelA rs7101916 T or RelB rs28372683 A was the potential protective factor against HCV infection among the Chinese population.