Tumor Necrosis Factor Alpha 308 G/A Single Nucleotide Polymorphism and Susceptibility to Hepatocellular Carcinoma Via Hepatitis B Infection

Abstract

Background: Hepatitis B virus (HBV) is a key factor for hepatocellular carcinoma (HCC). About 350 million people are affected by chronic infection which is related to the rapid development of liver diseases as well as hepatitis, cirrhosis and hepatocellular carcinoma. Expression of tumor necrosis factor alpha (TNFα) in the liver demonstrates a major genetic polymorphism which is involved in resistance or susceptibility to chronic HBV infection.

Materials and methods: In this study, two populations were studied by the sequence specific primerpolymerase chain reaction (SSPPCR) method: HBV cases (n=409), who were HBSAg+, and healthy controls (n=483).

Results: The results shown that the frequency of TNFα 308 G/G genotype in healthy controls (47.2%) was significantly higher than in HBV infected patients (28%) (CI = 1.292.61, OR = 1.83, P = 0.0004). Also TNFα 308 A/A and A/G genotype frequencies in the healthy controls were 4.6% and 48.2% and in patient group were 19.5% and 52.5% (CI = 2.237.12, p: 0.0001, OR: 3.94) respectively.

Conclusions: We found that among Iranian people TNFα 308A allele not only has the highest genotype frequency but also it has the highest frequency in the world population. In addition, TNFα308 G/G polymorphism was associated with HBV resistance, whereas TNFα308A (A/A or A/G) polymorphism appeared to associated with chronic HBV infection. These data suggested that among the Iranian population, the 308 G/G polymorphism of TNFα gene promoter region has the potential to influence the susceptibility to HBV infection and it may be responsible for viral antigen clearance.