Brief Genetics Report Large-Scale Association Studies of Variants in Genes Encoding the Pancreatic -Cell KATP Channel Subunits Kir6.2 (KCNJ11) and SUR1 (ABCC8) Confirm That the KCNJ11 E23K Variant Is Associated With Type 2 Diabetes

The genes ABCC8 and KCNJ11, which encode the sub-units sulfonylurea receptor 1 (SUR1) and inwardly rec-tifying potassium channel (Kir6.2) of the -cell ATP-sensitive potassium (KATP) channel, control insulin secretion. Common polymorphisms in these genes (ABCC8 exon 16–3t/c, exon 18 T/C, KCNJ11 E23K) have been variably associated with type 2 diabetes, but no large (2,000 subjects) case-control studies have been performed. We evaluated the role of these three variants by studying 2,486 U.K. subjects: 854 with type 2 diabetes, 1,182 population control subjects, and 150 parent-offspring type 2 diabetic trios. The E23K allele was associated with diabetes in the case-control study (odds ratio [OR] 1.18 [95 % CI 1.04–1.34], P 0.01) but did not show familial association with diabetes. Neithe