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

• 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
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.2004-1204

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.