The KCNJ11 E23K and ABCC8 exon 31 variants contribute to susceptibility to type 2 diabetes, glucose intolerance and altered insulin secretion in a Russian population

Aims: The KCNJ11 and ABCC8 genes encode components of the ATP-sensitive potassium (KATP) channel, which regulates insulin secretion by beta-cells. Alterations in the activity of pancreatic KATP could be involved in the pathogenesis of type 2 diabetes (T2D). We studied the KCNJ11 E23K and ABCC8 exon 31 variants for association with T2D, glucose intolerance and altered insulin secretion in a Russian population. Methods: Using a polymerase chain reaction (PCR) with the following digestion of a PCR product with a corresponding restriction enzyme, genomic DNA from Russian T2D patients (N = 127) and controls (N = 117) were genotyped. Fasting and 2 h glucose and insulin were measured in blood of all subjects studied. Biochemical parameters in diabetic and control individuals were compared by the unpaired Student's t-test. chi(2)-test was used to compare allele and genotype frequencies of the polymorphisms studied. Results: The KCNJ11 E23 variant and the ABCC8 exon 31 allele A were associated with higher risk of T2D (Odds Ratio (OR) of 1.53 (p = 0.023) and 2.41 (p = 1.95 x 10(-5)), respectively. T2D patients with the EE variant of KCNJ11 have elevated 2 h serum insulin (EE (87.3 +/- 34.9 mU/l) vs. KK + EK (82.1 +/- 31.1 mU/l), p = 0.038). Diabetic carriers of the ABCC8 G/G variant had reduced 2 h glucose compared to A/A + A/G (p = 0.031). The G/G genotype of ABCC8 was also significantly associated with increased both fasting and 2 h serum insulin in diabetic and non-diabetic patients. A HOMA-beta value characterizing the beta-cell homeostasis was higher in the non-diabetic carriers homozygous for G/G (98.0 +/- 46.9) than for other genotypes (HOMA-beta = 85.6 +/- 45.5 for A/A + A/G, p = 0.0015). Conclusions: The KCNJ11 E23K and ABCC8 exon31 variants contribute to susceptibility to T2D diabetes, glucose intolerance and altered insulin secretion in a Russian population. (C) 2008 Diabetes India. Published by Elsevier Ltd. All rights reserved.