Polymorphisms rs763110 in FASL is linked to hepatitis C virus infection among high-risk populations

ABSTRACT

Background

The Fas cell surface death receptor (FAS) and Fas ligand (FASL) can participate in the apoptosis of immune cells and target cells infected with a virus through the FAS-FASL signalling pathway. The decoy receptor 3 (DCR3) can competitively inhibit the binding of FAS to FASL. Our aim is to investigate the effect of single nucleotide polymorphisms (SNPs) in FAS, FASL and DCR3 on hepatitis C virus (HCV) infection.

Methods

Four SNPs (rs763110 in FASL, rs1324551 and rs2234767 in FAS and rs2257440 in DCR3) were genotyped in 1495 controls free of HCV, 522 individuals with spontaneous HCV clearance and 732 patients with hepatitis C virus infection. The RegulomeDB database and RNAfold web servers were used to explore potential biological functions of SNPs.

Results

FASL rs763110 was associated with susceptibility to HCV infection, and not to CHC. The odds ratio (95% confidence interval) of HCV infection in high-risk populations carrying FASL rs763110-TT was 1.82 (1.36–2.51, P < 0.001) compared to that of CC genotypes and 1.93 (1.43–2.60, P < 0.001) higher than that of CC + CT genotypes. Based on computer simulation, FASL rs763110-T may affect the transcription of mRNA by affecting the binding of a transcription factor, leading to structural changes in mRNA.

Conclusion

The genetic variant in FASL is linked with HCV infection, but not to spontaneous HCV clearance.

KEYWORDS:

• Hepatitis C Virus
• fas receptor
• fas ligand
• decoy receptor 3
• single nucleotide polymorphisms

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This study was supported by the National Natural Science Foundation of China (grant numbers: 81773499, 81703273), the Natural Science Foundation of Jiangsu Province of China (grant numbers: BK20171054), Science Foundation for Distinguished Young Scholars of Jiangsu (grant numbers: BK20190106), Jiangsu Program for Young Medical Talents (grant number: QNRC2016616) and Open Research Fund Program of the State Key Laboratory of Virology of China (No. 2019KF005).