Abstract
Aims/hypothesis. Non-alcoholic steatohepatitis is frequent in Type II (non-insulin-dependent) diabetes mellitus and can lead to fibrosis and cirrhosis. The interindividual variability in the occurrence of non-alcoholic steatohepatitis suggests, however, a genetic modulation. Microsomal triglyceride transfer protein (MTP) is necessary for the assembly and secretion of VLDL and when the protein is not functional, such as in abetalipoproteinaemia, a steatohepatitis occurs. 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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Received: 23 February 2000 and in revised form: 17 April 2000
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Bernard, S., Touzet, S., Personne, I. et al. Association between microsomal triglyceride transfer protein gene polymorphism and the biological features of liver steatosis in patients with Type II diabetes. Diabetologia 43, 995–999 (2000). https://doi.org/10.1007/s001250051481
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DOI: https://doi.org/10.1007/s001250051481