Lack of association between 4 key TNF-alpha promoter polymorphisms and hepatitis C virus infection in a population of Egyptian patients

Abstract

Introduction: With 170 million chronic hepatitis C virus (HCV) cases worldwide, HCV is considered a major life-threatening pathogen. HCV is a crucial causative of liver cirrhosis and hepatocellular carcinoma. Tumor necrosis factor-alpha (TNF-alpha) is thought to be a mediator in the development of viral hepatitis. Because HCV is epidemic in Egypt, this study aimed to characterize the distribution of TNF-alpha gene promoter polymorphisms and their relation to TNF-alpha expression in HCV patients. Methods: Four promoter polymorphisms; −1031T/C, −863C/A, −857C/T, and −308G/A, were studied by restriction fragment length polymorphism in a population of Egyptian HCV patients. Results: Compared to healthy subjects, none of these polymorphisms were associated with HCV infection. The wild-type −1031T, −863A, −857C, and −308G alleles were highly prevalent in the studied population. Sequencing the promoter region spanning the four studied polymorphisms in some subjects did not reveal any difference in the nucleotide variance pattern, compared with the TNF-alpha reference sequence. Relative TNF-alpha mRNA expressions in HCV patients and healthy subjects were statistically indifferent. Conclusion: Since previous studies confirmed an increase in TNF-alpha level in case of viral infections, this study focuses on mechanisms of post-transcriptional and posttranslational modifications of TNF-alpha gene in HCV patients, which decode the genetic factors linked to HCV infection and severity.