Genetic variations in the pancreatic ATP-sensitive potassium channel, β-cell dysfunction, and susceptibility to type 2 diabetes

• Published in: Acta diabetologica Vol. 46; no. 1; pp. 43 - 49
• Main Authors: Chistiakov, D. A., Potapov, V. A., Khodirev, D. C., Shamkhalova, M. S., Shestakova, M. V., Nosikov, V. V.
• Format: Journal Article
• Language: English
• Published: Milan Springer Milan 01.03.2009
• Subjects: ATP-Binding Cassette Transporters - genetics; Blood Glucose - metabolism; Diabetes; Diabetes Mellitus, Type 2 - epidemiology; Diabetes Mellitus, Type 2 - genetics; Diabetes Mellitus, Type 2 - physiopathology; DNA Primers; Exons; Gene Amplification; Genetic Predisposition to Disease; Genetic Variation; Humans; Insulin - blood; Insulin-Secreting Cells - physiology; Internal Medicine; Islets of Langerhans - physiopathology; Medicine; Medicine & Public Health; Metabolic Diseases; Moscow; Original Article; Polymerase Chain Reaction; Potassium Channels, Inwardly Rectifying - genetics; Receptors, Drug - genetics; Reference Values; Sulfonylurea Receptors; Type 2 diabetes; KCNJ11; ABCC8; Susceptibility
• ISSN: 0940-5429; 1432-5233
• DOI: 10.1007/s00592-008-0056-5

The KCNJ11 and ABCC8 genes encode the components of the pancreatic ATP-sensitive potassium (KATP) channel, which regulates insulin secretion by β-cells and hence could be involved in the pathogenesis of type 2 diabetes (T2D). The KCNJ11 E23K and ABCC8 exon 31 variants have been studied in 127 Russian T2D patients and 117 controls using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) approach. 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 × 10 −5 )], respectively. 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-β value characterizing the β-cell homeostasis was higher in the non-diabetic carriers homozygous for G/G (98.0 ± 46.9) then for other genotypes (HOMA-β = 85.6 ± 45.5 for A/A + A/G, P  = 0.0015). The KCNJ11 E23K and ABCC8 exon 31 variants contribute to susceptibility to T2D diabetes, glucose intolerance and altered insulin secretion in a Russian population.