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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.

Laukkanen O, Pihlajamäki J, Lindström J, Eriksson J, Valle TT, Hämäläinen H, Ilanne-Parikka P, Keinänen-Kiukaanniemi S, Tuomilehto J, Uusitupa M, Laakso M,

Department of Medicine, University of Kuopio, 70210 Kuopio, Finland.

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.

Published 6 December 2004 in J Clin Endocrinol Metab, 89(12): 6286-90.
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