Tumor necrosis factor-alpha -308G/A polymorphism and risk of hepatocellular carcinoma in hepatitis C virus-infected patients.
- Author:
Roba M TALAAT
1
;
Ahmed A ESMAIL
;
Reda ELWAKIL
;
Adel A GURGIS
;
Mahmoud I NASR
Author Information
- Publication Type:Journal Article
- MeSH: Adult; Aged; Alleles; Carcinoma, Hepatocellular; blood; genetics; virology; Female; Gene Frequency; Genetic Predisposition to Disease; Genotype; Hepatitis C, Chronic; blood; genetics; Humans; Liver Cirrhosis; blood; genetics; Liver Neoplasms; blood; genetics; virology; Male; Middle Aged; Polymorphism, Single Nucleotide; Real-Time Polymerase Chain Reaction; Risk Factors; Tumor Necrosis Factor-alpha; blood; genetics
- From:Chinese Journal of Cancer 2012;31(1):29-35
- CountryChina
- Language:English
- Abstract: Tumor necrosis factor-alpha (TNF-α) is an important cytokine in generating an immune response against infection with hepatitis C virus (HCV). The functions of TNF-α may be altered by single-nucleotide polymorphisms (SNPs) in its gene structure. We hypothesized that SNPs in TNF-α may be important in determining the outcome of an HCV infection. To test this hypothesis, we investigated the role of the polymorphism -308G/A, which is located in the promoter region of the TNF-α gene, in the progression of HCV infection in Egyptian patients using a quantitative real-time polymerase chain reaction (qRT-PCR). The distribution of this polymorphism and its impact on the serum level of TNF-α was compared between 90 HCV-infected patients [45 with HCV-induced cirrhosis and 45 with HCV-related hepatocellular carcinoma (HCC)] and 45 healthy Egyptian volunteers without any history of liver disease. Our results showed that at the TNF-α -308 position, the G/G allele was most common (78.5%) in the study population, with the G/A and A/A alleles occurring less frequently (13.3% and 8.1%, respectively). Frequencies of G/G, G/A, and A/A genotypes were 87%, 7%, and 6% in patients with liver cirrhosis and were 94%, 4%, and 2% in patients with HCC, respectively. Serum levels of TNF-α were significantly higher in HCV-infected patients than in healthy controls, indicating that the TNF-α -308 polymorphism does not influence the production of TNF-α. The serum level of TNF-α was positively correlated with HCV infection. Taken together, these findings suggest that the TNF-α -308 polymorphism may not be a host genetic factor associated with the severity of HCV infection, but may be an independent risk factor for HCC.
