The TNFRSF13B rs34562254 Polymorphism is Associated with Hepatitis C Infection Risk in the Han Chinese Population

Abstract Background Genetic variations in the tumor necrosis factor receptor superfamily (TNFRSF) 13B have been reported to be associated with immune-related diseases. This study aimed to explore the relationship of tumor necrosis factor superfamily (TNFSF) 13, TNFRSF13B, and TNFRSF14 missense mutations with hepatitis C virus (HCV) infection susceptibility. Methods Single-nucleotide polymorphisms (SNPs) in TNFSF13 (rs3803800, rs11552708), TNFRSF13B (rs34562254), and TNFRSF14 (rs4870) were genotyped in 469 intravenous drug users, 728 hemodialysis patients, and 1636 paid blood donors using a TaqMan real-time PCR assay. The USCS browser and RNAfold web servers were used to predict the biological functions of these selected SNPs. Results After adjusting for gender, age, levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and route of infection, a logistic regression analysis showed that subjects carrying a homozygous TNFRSF13B rs34562254 TT mutant were more likely to be infected by HCV compared to those homozygous with the rs34562254 CC wild type (co-dominant model: OR = 1.52, 95% CI: 1.17–1.98, P = 0.002; recession model: OR = 1.41, 95% CI: 1.10–1.81, P = 0.007; additive model: OR = 1.21, 95% CI: 1.07–1.37, P = 0.002). The effect of the risk allele rs34562254-T was stronger in subjects that were female, older (≥ 50 years old), paid blood donors, and with lower ALT and AST levels (≤ 40 U/L). A bioinformatics analysis via the UCSC genome browser found that rs34562254 was located at the highest peak of the H3K4Me1 histone marker. Using the RNAfold web servers, the minimum free energy of the centroid secondary structure was found to be higher for the mutant rs34562254-T allele (-38.90 kcal/mol) than its wild type C allele (-45.60 kcal/mol). Additionally, the RegulomeDB score of rs34562254 was 3a. Altogether, the results of the bioinformatics analysis indicate that rs34562254 may affect gene expression levels by regulating the transcriptional activity of corresponding gene regions. Conclusions The rs34562254 polymorphisms in TNFRSF13B were significantly associated with HCV infection among the Han Chinese population.