Influence of TNF gene polymorphisms in Japanese patients with NASH and simple steatosis.
OBJECTIVE
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.
Tokushige
Katsutoshi
K
Tokyo Women's Medical University, Department of Medicine and Gastroenterology, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan. ktoku@pg7.so-net.ne.jp
Takakura
Mihoko
M
Tsuchiya-Matsushita
Noriko
N
Taniai
Makiko
M
Hashimoto
Etsuko
E
Shiratori
Keiko
K
D000328:Adult; D001706:Biopsy; D005234:Fatty Liver / Q000235:genetics*; D005260:Female; D005355:Fibrosis; D006239:Haplotypes; D006801:Humans; D007564:Japan; D008107:Liver Diseases / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D018124:Receptors, Tumor Necrosis Factor; D047889:Receptors, Tumor Necrosis Factor, Type II; D014409:Tumor Necrosis Factor-alpha