Polymorphisms of the SUR1 (ABCC8) and Kir6.2 (KCNJ11) Genes Predict the Conversion from Impaired Glucose Tolerance to Type 2 Diabetes. The Finnish Diabetes Prevention Study

Type 2 diabetes is caused by defective insulin secretion and impaired insulin action. We investigated whether common polymorphisms in the SUR1 and Kir6.2 genes are associated with increased risk of type 2 diabetes in 490 subjects with impaired glucose tolerance participating in the Finnish Diabetes...

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Published in:The journal of clinical endocrinology and metabolism 2004-12, Vol.89 (12), p.6286-6290
Main Authors: Laukkanen, Olli, Pihlajamäki, Jussi, Lindström, Jaana, Eriksson, Johan, Valle, Timo T, Hämäläinen, Helena, Ilanne-Parikka, Pirjo, Keinänen-Kiukaanniemi, Sirkka, Tuomilehto, Jaakko, Uusitupa, Matti, Laakso, Markku
Format: Article
Language:English
Subjects:
Adenine
Adult
Alleles
ATP-Binding Cassette Transporters - genetics
Biological and medical sciences
Confidence Intervals
Diabetes Mellitus, Type 2 - etiology
Diabetes. Impaired glucose tolerance
Disease Progression
Endocrine pancreas. Apud cells (diseases)
Endocrinopathies
Etiopathogenesis. Screening. Investigations. Target tissue resistance
Fundamental and applied biological sciences. Psychology
Genetic Predisposition to Disease
Glucose Intolerance - complications
Guanine
Haplotypes
Humans
Linkage Disequilibrium
Lysine
Medical sciences
Middle Aged
Odds Ratio
Polymorphism, Genetic
Potassium Channels - genetics
Potassium Channels, Inwardly Rectifying - genetics
Promoter Regions, Genetic - genetics
Receptors, Drug - genetics
Sulfonylurea Receptors
Vertebrates: endocrinology
Citations: Items that cite this one
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Summary:Type 2 diabetes is caused by defective insulin secretion and impaired insulin action. We investigated whether common polymorphisms in the SUR1 and Kir6.2 genes are associated with increased risk of type 2 diabetes in 490 subjects with impaired glucose tolerance participating in the Finnish Diabetes Prevention Study. The 1273AGA allele of the SUR1 gene was associated with a 2-fold risk of type 2 diabetes [odds ratio (OR), 2.00; 95% confidence interval (CI), 1.19–3.36; P = 0.009]. This silent polymorphism was in linkage disequilibrium with three promoter polymorphisms (G-2886A, G-1561A, and A-1273G), and they formed a high-risk haplotype having a 2-fold risk of type 2 diabetes (OR, 1.89; 95% CI, 1.09–3.27; P = 0.023). Subjects with both the high-risk haplotype of the SUR1 gene and the 23K allele of the Kir6.2 gene had a 6-fold risk for the conversion to diabetes compared with those without any of these risk genotypes (OR, 5.68; 95% CI, 1.75–18.32; P = 0.004). We conclude that the polymorphisms of the SUR1 gene predicted the conversion from impaired glucose tolerance to type 2 diabetes and that the effect of these polymorphisms on diabetes risk was additive with the E23K polymorphism of the Kir6.2 gene.
ISSN:0021-972X
1945-7197
DOI:10.1210/jc.2004-1204