Genetic Variation on TNF/LTA and TNFRSF1A Genes is Associated with Outcomes of Hepatitis C Virus Infection

ABSTRACT

Hepatitis C virus (HCV) infections are a serious global-scaled public health problem. Tumor necrosis factor (TNF)/lymphotoxin alpha (LTA) has been found to play a crucial role in relation to the outcomes of HCV infection after it binds to TNF receptor superfamily member 1A (TNFRSF1A). Thus, we investigated whether or not the TNF/LTA gene cluster and TNFRSF1A gene polymorphisms were associated with the outcomes of HCV infection. 1103 control participants without HCV infection, 497 patients with spontaneous clearance of HCV infection, and 713 patients with persistent HCV infection were enrolled. Rs2229094, rs1041981, rs1799964, and rs767455 were genotyped using the ABI TaqMan allelic discrimination assay. After adjusting for age, gender, and after determining a high-risk population, we used logistic regression analyses for which results indicated that the rs767455-C allele was associated with a reduced risk of HCV infection compared to respective results for the wild-type T allele (dominant model: adjusted OR = 0.74, 95% CI = 0.60–0.92, P = .006; additive model: adjusted OR = 0.76, 95% CI = 0.62–0.91, P = .004). Results also indicated that the rs1041981-A allele was associated with a decreased risk of persistent HCV infection compared to respective results for the wild-type C allele (additive model: adjusted OR = 0.81, 95% CI = 0.68–0.96, P = .017). Genetic polymorphisms in the LTA and TNFRSF1A genes were found to have been potentially important in relation to the susceptibility and chronicity of HCV infection among Chinese Han population.

KEYWORDS:

• Tumor necrosis factor
• lymphotoxin alpha
• single nucleotide polymorphism
• chronic

Author contributions

M.Y. and W.H. conceived and designed the experiments; H.F., T.T, Z.F. and J.W. performed the experiments; M.Y., F.L. and C.W. analyzed the data; X.X., P.Z., J.L., Y.H. and Y.Z. contributed reagents/materials/analysis tools; M.Y. and W.H. wrote the paper. All authors read and approved the final manuscript.

Disclosure statement

The authors declare no conflict of interest.

Supplementary material

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Additional information

Funding

This work was supported by Open Research Fund Program of the State Key Laboratory of Virology of China [No. 2019KF005]; the National Natural Science Foundation of China [81773499]; Science Foundation for Distinguished Young Scholars of Jiangsu Province [BK20190106]; Key Project of Natural Science Foundation of Yunnan Province [2019FA005].