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 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.
Laukkanen
Olli
O
Department of Medicine, University of Kuopio, 70210 Kuopio, Finland.
Pihlajamäki
Jussi
J
Lindström
Jaana
J
Eriksson
Johan
J
Valle
Timo T
TT
Hämäläinen
Helena
H
Ilanne-Parikka
Pirjo
P
Keinänen-Kiukaanniemi
Sirkka
S
Tuomilehto
Jaakko
J
Uusitupa
Matti
M
Laakso
Markku
M
D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000225:Adenine; D000328:Adult; D000483:Alleles; D016001:Confidence Intervals; D003924:Diabetes Mellitus, Type 2 / Q000209:etiology*; D018450:Disease Progression; D020022:Genetic Predisposition to Disease; D018149:Glucose Intolerance / Q000150:complications*; D006147:Guanine; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008239:Lysine; D008875:Middle Aged; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D015221:Potassium Channels / Q000235:genetics*; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics; D011955:Receptors, Drug / Q000235:genetics*; D064233:Sulfonylurea Receptors; D000099161:Kcnj11 Channel
D018528:ATP-Binding Cassette Transporters; D000225:Adenine; D006147:Guanine; D008239:Lysine; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D011955:Receptors, Drug; D064233:Sulfonylurea Receptors; D000099161:Kcnj11 Channel; C577507:ABCC8 protein, human