Association between microsomal triglyceride transfer protein gene polymorphism and the biological features of liver steatosis in patients with type II diabetes

Diabetologia. 2000 Aug;43(8):995-9. doi: 10.1007/s001250051481.

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 nonalcoholic 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.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Apolipoproteins / genetics
  • Carrier Proteins / genetics*
  • Cholesterol Ester Transfer Proteins
  • Diabetes Mellitus, Type 2 / complications*
  • Diabetes Mellitus, Type 2 / genetics*
  • Diabetes Mellitus, Type 2 / physiopathology
  • Female
  • France
  • Genotype
  • Glycoproteins*
  • Hepatitis, Chronic / etiology*
  • Hepatitis, Chronic / genetics
  • Hepatitis, Chronic / physiopathology
  • Humans
  • Liver / diagnostic imaging
  • Liver Function Tests
  • Male
  • Middle Aged
  • Polymerase Chain Reaction
  • Polymorphism, Genetic*
  • Polymorphism, Restriction Fragment Length
  • Promoter Regions, Genetic*
  • Ultrasonography
  • Whites

Substances

  • Apolipoproteins
  • CETP protein, human
  • Carrier Proteins
  • Cholesterol Ester Transfer Proteins
  • Glycoproteins