The term non-alcoholic steatohepatitis (NASH) describes liver disease histologically similar to alcoholic liver disease occurring in patients without any history of excessive alcohol consumption [1,2]. Two main histological criteria are necessary for the diagnosis of NASH: fatty degeneration and inflammation or fibrosis. The latter criteria distinguishes NASH from simple steatosis which has a non-progressive course [3]. In western countries, NASH is a major cause of increased liver enzymes, next to alcohol consumption and hepatitis C [2]. It is frequently associated with obesity (40 %), Type II diabetes (20 %) and hyperlipidaemia (20 %) We therefore assessed the association between a functional polymorphism in the promoter region of MTP gene (±493 G/T) and the biological features of steatohepatitis in Type II diabetic patients. Methods. We studied 271 patients with Type II diabetes. Determination of ±493 G/T polymorphism was made by PCR-RFLP. Increased liver enzymes were used as surrogates of liver steatosis and alanine aminotransferase concentration was the outcome variable for the multivariate analysis. Liver ultrasonography was available for a subgroup of patients with newly diagnosed diabetes.Results. The proportion of patients with increased alanine aminotransferase was higher in GG than in GT and TT subgroups (23 %, 11 % and 6 %, respectively, p = 0.01). Additionally, patients with high alanine aminotransferase concentrations were more likely to be young (p = 0.01), male (p = 0.001), obese (p = 0.04) and have low HDL-cholesterol (p = 0.01).In multivariate analysis, the MTP genotype was independently associated with alanine aminotransferase concentration (p = 0.0023) as well as sex and body mass index but not HDL-cholesterol. Conclusion/interpretation. The ±493 G/T MTP gene polymorphism is associated with biological surrogates of steatohepatitis in patients with Type II diabetes. The G allele which is responsible for a decrease in MTP gene transcription is prone to increase the intrahepatic triglycerides content, conferring by this a genetic susceptibility for steatohepatitis. [Diabetologia (2000) 43: 995±999]
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