P Huang1,2, C H Wang2, L Y Zhuo1, X S Xia3, S Yang4, J W Zhang5, H Z Fan6, J J Wu1, R Yu1, M Yue7,8, Y Zhang1,2. 1. Department of Epidemiology and Biostatistics, Key Laboratory of Infectious Diseases, Nanjing Medical University , Nanjing, China. 2. Institute of Epidemiology and Microbiology, Eastern Theater Command Centers for Disease Control and Prevention , Nanjing, China. 3. College of Life Science and Technology, Kunming University of Science and Technology , Kunming, China. 4. Department of Biostatistics, School of Public Health, Nanjing Medical University , Nanjing, China. 5. Department of Anesthesiology, Affiliated Drum-Tower Hospital of Medical College of Nanjing University , Jiangsu, China. 6. Department of Information, The First Affiliated Hospital of Nanjing Medical University , Nanjing, China. 7. Department of Infectious Diseases, The First Affiliated Hospital of Nanjing Medical University , Nanjing, China. 8. State Key Laboratory of Virology, School of Basic Medical Sciences, Wuhan University , Wuhan, China.
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.
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:FASLrs763110 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 FASLrs763110-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, FASLrs763110-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.
Entities:
Keywords:
Hepatitis C Virus; decoy receptor 3; fas ligand; fas receptor; single nucleotide polymorphisms