Tumor necrosis factor-alpha -308G/A polymorphism and risk of hepatocellular carcinoma in hepatitis C virus-infected patients.
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.
Molecular Biology Department, Menofia University, Sadat, Egypt. Robamtalaat@yahoo.com
Roba M
RM
Talaat
Ahmed A
AA
Esmail
Reda
R
Elwakil
Adel A
AA
Gurgis
Mahmoud I
MI
Nasr
D000328:Adult; D000368:Aged; D000483:Alleles; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000235:genetics* / Q000821:virology; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D019698:Hepatitis C, Chronic / Q000097:blood / Q000235:genetics*; D006801:Humans; D008103:Liver Cirrhosis / Q000097:blood / Q000235:genetics; D008113:Liver Neoplasms / Q000097:blood / Q000235:genetics* / Q000821:virology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D060888:Real-Time Polymerase Chain Reaction; D012307:Risk Factors; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000235:genetics*
D014409:Tumor Necrosis Factor-alpha