Genetic Variants in TNFSF4 and TNFSF8 Are Associated With the Risk of HCV Infection Among Chinese High-Risk Population.

Zuqiang Fu,Peng Huang,Ming Yue,Jinwei Zhang,Chao Shen,Haozhi Fan,Weihua Cai,Zhijun Ge,Chen Dong,Hong Xue,Yun Zhang,Jianguo Shao,Chunhui Wang

doi:10.3389/fgene.2021.630310

Abstract

BackgroundThe tumor necrosis factor superfamily (TNFSF) and TNF receptor superfamily (TNFRSF) play important roles in the immune responses to infections. The aim of this study was to determine the impact of single nucleotide polymorphisms (SNPs) of several TNFSF/TNFRSF genes on the risk of hepatitis C virus (HCV) infection in the Chinese high-risk population.MethodsThe TNFSF4-rs1234313, TNFSF4-rs7514229, TNFSF8-rs3181366, TNFSF8-rs2295800, TNFRSF8-rs2298209, and TNFRSF8-rs2230625 SNPs were genotyped in 2309 uninfected controls, 597 subjects with spontaneous HCV clearance and 784 patients with persistent HCV infection using the TaqMan-MGB assay. The putative functions of the positive SNPs were determined using online bioinformatics tools.ResultsAfter adjusting for gender, age, high-risk population, alanine transaminase (ALT), aspartate aminotransferase (AST), IL28B-rs12979860 and rs8099917 genotypes, the non-conditional logistic regression showed that rs7514229-T, rs3181366-T, and rs2295800-C were associated with an increased risk of HCV infection (all PFDR < 0.05). Combined analysis of rs7514229-T and rs3181366-T risk alleles showed that the subjects carrying 2–4 risk alleles were more susceptible to HCV infection compared with those lacking any risk allele (all P < 0.001). Furthermore, the risk of HCV infection increased with the number of risk alleles (Ptrend < 0.001). In silico analysis showed that rs7514229, rs3181366, and rs2295800 polymorphisms may affect the transcription of mRNA by regulating miRNA binding, TF binding, and promoter activation, respectively, which may have biological consequences.ConclusionTNFSF4-rs7514229, TNFSF8-rs3181366, and TNFSF8-rs2295800 are associated with increased risk of HCV infection in the Chinese high-risk population.

Highlights

MATERIALS AND METHODSHepatitis C is the result of hepatitis C virus (HCV) infection and currently afflicts around 185 million people worldwide, of which 71 million are chronically infected (WHO, 2018; Spearman et al, 2019)
After adjusting for gender, age, high-risk population, alanine transaminase (ALT), aspartate aminotransferase (AST), IL28B-rs12979860 and rs8099917 genotypes, the non-conditional logistic regression showed that rs7514229-T, rs3181366-T, and rs2295800-C were associated with an increased risk of HCV infection
Combined analysis of rs7514229-T and rs3181366-T risk alleles showed that the subjects carrying 2–4 risk alleles were more susceptible to HCV infection compared with those lacking any risk allele

Summary

Introduction

MATERIALS AND METHODSHepatitis C is the result of hepatitis C virus (HCV) infection and currently afflicts around 185 million people worldwide, of which 71 million are chronically infected (WHO, 2018; Spearman et al, 2019). WHO and other international organizations have pledged to eliminate HCV infection by 2030, which is incumbent on the development of effective vaccines and therapeutics (WHO, 2018). Direct-acting antiviral drugs (DAAs) have been effective against HCV, only 1.3% of the patients in China have received these drugs owing to their high costs (Wei et al, 2016; Li and Chung, 2019). The attempts to develop an HCV vaccine have been largely unsuccessful due to the high genetic variability of this virus. The aim of this study was to determine the impact of single nucleotide polymorphisms (SNPs) of several TNFSF/TNFRSF genes on the risk of hepatitis C virus (HCV) infection in the Chinese high-risk population

Objectives

Results

Conclusion