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

Ahmed M Ghoneim

doi:10.15419/bmrat.v6i5.542

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.

Highlights

With 170 million chronic hepatitis C virus (HCV) cases worldwide, HCV is considered a major life-threatening pathogen
To investigate whether there is an association between Tumor necrosis factor-α (TNF-α) gene polymorphisms and the risk of infection with HCV, DNA was extracted from the blood of 50 HCV RNA positive-patients and 50 healthy subjects, and TNF-α gene promoter was investigated by RFLP technique for the presence of 4 different polymorphisms; −1031T/C, −863C/A, −857C/T, and −308G/A
For −1031T/C polymorphism, the homozygous wild TT genotype was detected in 50% of the HCV patients and 60% of the healthy subjects, while the heterozygous TC genotype was detected in 44% of HCV patients and 34% of healthy subjects

Summary

Introduction

With 170 million chronic hepatitis C virus (HCV) cases worldwide, HCV is considered a major life-threatening pathogen. Because HCV is epidemic in Egypt, this study aimed to characterize the distribution of TNF-α gene promoter polymorphisms and their relation to TNF-α expression in HCV patients. The Hepatitis C virus (HCV) is the major cause of liver cirrhosis and hepatocellular carcinoma (HCC), which is the most common causative of liver transplantation in several countries 1. Chronic liver inflammation develops by the aid of various mediators, which may act as cofactors in carcinogenesis 3 Among these mediators, the tumor necrosis factor-α (TNF-α) is a critical pathogenic mediator in the development of viral hepatitis. TNF-α is required for the propagation of liver cells in case of liver damage

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