The G-250A substitution in the promoter region of the hepatic lipase gene is associated with the conversion from impaired glucose tolerance to type 2 diabetes: the STOP-NIDDM trial

J Intern Med. 2005 Feb;257(2):185-93. doi: 10.1111/j.1365-2796.2004.01435.x.

Abstract

Objectives: Dyslipidaemia that includes high levels of triglycerides and low high-density lipoprotein cholesterol is a risk factor for type 2 diabetes. Hepatic lipase gene encoding a lipolytic enzyme participating in remodelling of plasma lipoproteins and formation of serum lipid profile is a promising candidate gene for type 2 diabetes. The purpose of the study was to investigate whether the G-250A promoter polymorphism of the LIPC gene predicts the conversion from impaired glucose tolerance (IGT) to type 2 diabetes.

Subjects and design: Study population comprised of subjects who participated in the STOP-NIDDM trial aiming to investigate the effect of acarbose compared with placebo on the prevention of type 2 diabetes in subjects with IGT.

Results: Compared with subjects carrying the G-250G genotype, subjects with the A-250A genotype of the LIPC gene had a 2.35-fold [95% confidence interval (CI) 1.27-4.33, P = 0.006] higher risk of developing type 2 diabetes. Subjects in the placebo group and all women carrying the A-250A genotype had an especially high risk for the conversion to type 2 diabetes [odds ratio (OR) 2.74, 95% CI 1.14-6.61, P = 0.024 and OR 3.70, 95% CI 1.35-10.1, P = 0.011 respectively].

Conclusion: The G-250A promoter polymorphism of the LIPC gene is associated with an increased risk of development of type 2 diabetes in high-risk subjects with IGT. Therefore, genes regulating atherogenic dyslipidaemia are promising candidate genes for type 2 diabetes.

Publication types

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

MeSH terms

  • Chi-Square Distribution
  • Diabetes Mellitus, Type 2 / enzymology
  • Diabetes Mellitus, Type 2 / genetics*
  • Female
  • Genotype
  • Humans
  • Lipase / genetics*
  • Liver / enzymology
  • Male
  • Middle Aged
  • Polymorphism, Genetic*
  • Promoter Regions, Genetic / genetics*
  • Randomized Controlled Trials as Topic
  • Risk

Substances

  • LIPC protein, human
  • Lipase