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.
OBJECTIVE
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.


METHODS
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].


CONCLUSIONS
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.
Zacharova
J
J
Department of Medicine, University of Kuopio, Kuopio, Finland.
Todorova
B R
BR
Chiasson
J-L
JL
Laakso
M
M
D016009:Chi-Square Distribution; D003924:Diabetes Mellitus, Type 2 / Q000201:enzymology / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008049:Lipase / Q000235:genetics*; D008099:Liver / Q000201:enzymology; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics*; D016032:Randomized Controlled Trials as Topic; D012306:Risk
C504173:LIPC protein, human; D008049:Lipase