title: The G-250A promoter polymorphism of the hepatic lipase gene predicts the conversion from impaired glucose tolerance to type 2 diabetes mellitus: the Finnish Diabetes Prevention Study.
abstract: In population-based studies, dyslipidemia related to insulin resistance (high triglyceride level and low high-density lipoprotein cholesterol level) is a risk factor for type 2 diabetes. Therefore, variants in genes regulating lipid and lipoprotein metabolism are potential candidate genes for diabetes. We investigated whether the G-250A polymorphism of the hepatic lipase gene (LIPC) predicts the conversion from impaired glucose tolerance (IGT) to type 2 diabetes in the Finnish Diabetes Prevention Study. This study randomized subjects to either the intervention group (lifestyle modification aimed at weight loss, such as changes in diet and increased physical exercise) or the control group. Genotyping at position -250 of the LIPC gene was performed with PCR amplification, DraI enzyme digestion, and gel electrophoresis in 490 subjects with IGT whose DNA was available. In the entire study population, the conversion rate to type 2 diabetes was 17.8% among subjects with the G-250G genotype and 10.7% among subjects with the -250A allele (P = 0.032). In univariate analysis, the odds ratio for the G-250G genotype to predict the conversion from IGT to type 2 diabetes was 1.80 (95% confidence interval, 1.05-3.10; P = 0.034). In multivariate logistic regression analysis, the G-250G genotype predicted the conversion to diabetes independently of the study group (control or intervention), gender, weight, waist circumference at baseline, and change in weight and waist circumference. In the intervention group, 13.0% of subjects with the G-250G genotype and 1.0% of the subjects with the -250A allele converted to diabetes (P = 0.001). We conclude that the G-250G genotype of the LIPC gene is a risk factor for type 2 diabetes. Therefore, genes regulating lipid and lipoprotein metabolism may be potential candidate genes for type 2 diabetes.
authors.affiliation: Department of Medicine, University of Kuopio, 70210 Kuopio.
authors.forename: Boryana
authors.initials: B
authors.lastname: Todorova
authors.forename: Agata
authors.initials: A
authors.lastname: Kubaszek
authors.forename: Jussi
authors.initials: J
authors.lastname: Pihlajamäki
authors.forename: Jaana
authors.initials: J
authors.lastname: Lindström
authors.forename: Johan
authors.initials: J
authors.lastname: Eriksson
authors.forename: Timo T
authors.initials: TT
authors.lastname: Valle
authors.forename: Helena
authors.initials: H
authors.lastname: Hämäläinen
authors.forename: Pirjo
authors.initials: P
authors.lastname: Ilanne-Parikka
authors.forename: Sirkka
authors.initials: S
authors.lastname: Keinänen-Kiukaanniemi
authors.forename: Jaakko
authors.initials: J
authors.lastname: Tuomilehto
authors.forename: Matti
authors.initials: M
authors.lastname: Uusitupa
authors.forename: Markku
authors.initials: M
authors.lastname: Laakso
mesh_terms: D000483:Alleles; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D018450:Disease Progression; D015444:Exercise; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D018149:Glucose Intolerance / Q000178:diet therapy / Q000235:genetics* / Q000628:therapy; D006801:Humans; D008019:Life Style; D008049:Lipase / Q000235:genetics*; D008099:Liver / Q000201:enzymology*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics*; D015431:Weight Loss
chemical_list: D008049:Lipase