TNF-related apoptosis-inducing ligand (TRAIL), death receptor (DR4) and Fas gene polymorphisms associated with liver cirrhosis in hepatitis C infected patients

Abstract

Host genetic factors of apoptotic genes could play an important role in the rapid progression of chronic hepatitis C virus (HCV) infection to liver cirrhosis. This study focused on the role of Tumor Necrosis Factor Related Apoptosis-Inducing Ligand (TRAIL) (1525G/A and 1595C/T), TRAIL Death Receptor4 (DR4) (626C/G and 683A/C) and Fas (−670A/G and −1377G/A) genetic polymorphisms in the susceptibility of HCV infected patients to develop liver cirrhosis. Genotyping was performed by restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR) in 69 cirrhotic and106 non-cirrhotic patients. Association of selected genes with response to various direct-acting anti-viral drugs was demonstrated. Our data showed an increase in TRAIL (1525AA and 1595TT), DR4 (626CC, 683AA, and 683CC) genotypes, and the DR4 683A allele in cirrhotic patients. However, no statistical significance in their distribution was found indicating the lack of association between these SNPs and liver cirrhosis susceptibility in HCV-infected patients. The genotype frequencies of TRAIL at loci 1525 and 1595 appeared to be in complete linkage disequilibrium (D'= 0.9997, r2= 0.9994). Concerning treatment, a significant elevation in AA genotype and A allele of DR4 (683A/C) was found. The outcome of this study reveals that, in our population group, no association between apoptotic genes polymorphism and susceptibility to HCV-related liver cirrhosis. Studies concerning other apoptosis gene polymorphisms are required to get a better understanding of the development of cirrhosis in HCV-infected patients and to help in limiting HCV complications and improve the management and treatment services.