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

J Clin Endocrinol Metab. 2004 Dec;89(12):6286-90. 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.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP-Binding Cassette Transporters / genetics*
  • Adenine
  • Adult
  • Alleles
  • Confidence Intervals
  • Diabetes Mellitus, Type 2 / etiology*
  • Disease Progression
  • Genetic Predisposition to Disease
  • Glucose Intolerance / complications*
  • Guanine
  • Haplotypes
  • Humans
  • Linkage Disequilibrium
  • Lysine
  • Middle Aged
  • Odds Ratio
  • Polymorphism, Genetic*
  • Potassium Channels / genetics*
  • Potassium Channels, Inwardly Rectifying / genetics*
  • Promoter Regions, Genetic / genetics
  • Receptors, Drug / genetics*
  • Sulfonylurea Receptors


  • ABCC8 protein, human
  • ATP-Binding Cassette Transporters
  • Kir6.2 channel
  • Potassium Channels
  • Potassium Channels, Inwardly Rectifying
  • Receptors, Drug
  • Sulfonylurea Receptors
  • Guanine
  • Adenine
  • Lysine