Association of tumor necrosis factor-alpha gene promoter polymorphisms with acute viral hepatitis in the Indian population

Abstract

The key elements that determine the host response to either the self-limited or a severe fulminant form of liver disease are unclear. We have investigated the potential association of single nucleotide polymorphisms (SNPs) in the promoter region of tumor necrosis factor-alpha (TNFalpha) in their susceptibility to acute viral hepatitis (AVH) and fulminant hepatic failure (FHF) patients exhibiting specific viral etiology. A total of 124 individuals including 64 cases comprising 27 FHF, 37 AVH, and 60 healthy controls were recruited. SNPs at -238 (G/A), -308 (G/A), -857 (C/T), and -863 (C/A) of TNFalpha were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and confirmed by direct sequencing. Serum levels of TNFalpha were determined at admission and death or recovery. Association between the TNFalpha genotype and susceptibility to FHF was not evident; however, carrier genotypes in relation to the -308 (GA/AA) and -857 (CT/TT) loci were found to be significantly (P < or = 0.05) associated with susceptibility to AVH in relation to controls. The mean TNFalpha serum levels at admission were significantly higher (P < 0.001) in FHF than AVH patients, but no marked difference was observed between FHF-E (expired; n = 17) and FHF-S (survivors; n = 10), though the former were comparatively higher. This study suggests that SNPs at -308 and -857 of the TNFalpha promoter may represent an increased risk for the development of AVH but not for FHF in the Indian population.