Genetic variations in the pancreatic ATP-sensitive potassium channel, beta-cell dysfunction, and susceptibility to type 2 diabetes.
The KCNJ11 and ABCC8 genes encode the components of the pancreatic ATP-sensitive potassium (KATP) channel, which regulates insulin secretion by beta-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 x 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-beta value characterizing the beta-cell homeostasis was higher in the non-diabetic carriers homozygous for G/G (98.0+/-46.9) then for other genotypes (HOMA-beta = 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.
Chistiakov
D A
DA
Department of Pathology, University of Pittsburgh, A709 Scaife Hall, 3550 Terrace St, Pittsburgh, PA 15261, USA. dimitry.chistiakov@eudoramail.com
Potapov
V A
VA
Khodirev
D C
DC
Shamkhalova
M S
MS
Shestakova
M V
MV
Nosikov
V V
VV