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

. 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.