Polymorphism Rs34562254 In TNFRSF13B is Associated with HCV Infection Outcomes Among Chinese Han Population

Abstract Genetic variations in tumor necrosis factor receptor superfamily (TNFRSF) 13B have already proved 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 the susceptibility of HCV infection. 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 by TaqMan real-time PCR assay. And the USCS Brower and RNAfold web servers were used to predict the potential biological functions of the positive SNPs. After adjustment for gender, age, ALT level, AST level and route of infection, the results of logistic regression analysis showed that the subjects carried rs34562254 TT mutant homozygous type in TNFRSF13B were more likely to be infected by HCV compared to those with rs34562254 CC wild homozygous 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). And the effect of the risk allele (rs34562254-T) is more evident in female, elder (≥ 50), paid blood donors, lower ALT level (≤ 40 U/L) and lower ALT level (≤ 40 U/L) subgroup. The result of bioinformatics analysis showed that rs34562254 was located at the highest peak of the H3K4Me1 histone marker with the UCSC genome browser. And the minimum free energy (MFE) of the centroid secondary structure for the mutant T allele (-38.90 kcal/mol) of rs34562254 was higher than that of the wild C allele (-45.60 kcal/mol) with the RNAfold web servers. In addition, the RegulomeDB score of rs34562254 was 3a with the RegulomeDB web servers. All the above results of bioinformatics analysis suggested that rs34562254 may affect the gene expression level by regulating the transcriptional activity of the corresponding gene region. The rs34562254 polymorphisms in TNFRSF13B were significantly associated with HCV infection among Chinese Han population.