Influence of TNF gene polymorphisms in Japanese patients with NASH and simple steatosis

BACKGROUND/AIMS: Tumor necrosis factor (TNF) is considered to play a role in the second hit of non-alcoholic steatohepatitis (NASH). To clarify the effects of TNF in NASH we investigated TNF gene polymorphisms that might influence TNF production were investigated. METHODS: We analyzed 102 patients with non-alcoholic fatty liver disease (NAFLD; 36 with simple steatosis and 66 with NASH) and 100 control subjects. The serum level of soluble TNF receptor (sTNFR)-2 was measured. The TNF-alpha promoter region positions -1031, -863, -857, -308, and -238 and the TNF-beta gene Nco1 polymorphism site were investigated. RESULTS: The level of sTNFR-2 was significantly higher in NASH patients than in those with simple steatosis or control subjects. In the analysis of TNF gene polymorphisms, there were no significant deviations between the group of all NAFLD patients and the control subjects. The carrier frequencies of polymorphisms at positions -1031C and -863A were significantly higher in patients with NASH than in those with simple steatosis. In the multivariate analysis, TNF-alpha promoter polymorphisms proved to be significant independent factors distinguishing NASH from simple steatosis. CONCLUSIONS: TNF polymorphisms, which influence TNF production, might be associated with the progression of NAFLD.