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

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

JOURNAL=Frontiers in Genetics

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2021.630310

DOI=10.3389/fgene.2021.630310

ISSN=1664-8021

ABSTRACT=<sec><title>Background</title><p>The tumor necrosis factor superfamily (<italic>TNFSF</italic>) and TNF receptor superfamily (<italic>TNFRSF</italic>) 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 <italic>TNFSF/TNFRSF</italic> genes on the risk of hepatitis C virus (HCV) infection in the Chinese high-risk population.</p></sec><sec><title>Methods</title><p>The <italic>TNFSF4</italic>-rs1234313, <italic>TNFSF4</italic>-rs7514229, <italic>TNFSF8</italic>-rs3181366, <italic>TNFSF8</italic>-rs2295800, <italic>TNFRSF8</italic>-rs2298209, and <italic>TNFRSF8</italic>-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.</p></sec><sec><title>Results</title><p>After adjusting for gender, age, high-risk population, alanine transaminase (ALT), aspartate aminotransferase (AST), <italic>IL28B</italic>-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 <italic>P<sub><italic>FDR</italic></sub></italic> &lt; 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 <italic>P</italic> &lt; 0.001). Furthermore, the risk of HCV infection increased with the number of risk alleles (<italic>P<sub><italic>trend</italic></sub></italic> &lt; 0.001). <italic>In silico</italic> 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.</p></sec><sec><title>Conclusion</title><p><italic>TNFSF4</italic>-rs7514229, <italic>TNFSF8</italic>-rs3181366, and <italic>TNFSF8</italic>-rs2295800 are associated with increased risk of HCV infection in the Chinese high-risk population.</p></sec>