Association of sulfonylurea receptor 1 genotype with therapeutic response to gliclazide in type 2 diabetes

Pharmacogenomic analysis of ATP-sensitive potassium channels coexpressing the common type 2 diabetes risk variants E23K and S1369A

“…Furthermore, normoglycemic carriers of the K23/A1369 risk haplotype have been shown to have diminished insulin secretory function in response to a glucose challenge [9,15]. Interestingly, several recent clinical studies have demonstrated that individuals homozygous for the K23/A1369 risk haplotype display a higher therapeutic efficacy to the sulfonylurea gliclazide compared with the E23/S1369 nonrisk haplotype [16,17], although whether this is a direct effect of the haplotype itself was not determined. However, our recent study [4] provided the first direct evidence at the single channel level that K ATP channels containing the K23/A1369 risk haplotype display an increased sensitivity to gliclazide that was conferred by the presence of the A1369 variant (IC 50 for E23/S1369 vs. K23/ A1369 = 188.7 ± 32.6 vs. 52.7 ± 11.1 nmol/l).…”

Metabolic Control in Type 2 Diabetes Is Associated with Sulfonylurea Receptor-1 (SUR-1) but Not with KCNJ11 Polymorphisms

“…Numerous polymorphisms of these genes are reported in association with susceptibility to type 2 diabetes and diabetic phenotypes (5,6,7). These polymorphisms may lead to a loss of activity of potassium channel and to uncontrolled over secretion of insulin (2), as well as modulated response to sulfonylurea therapy (8,9).…”

Replication of association between polymorphisms of the pancreatic ATP-sensitive potassium channel and susceptibility to type 2 diabetes in two Russian urban populations

“…Several reports showed association between the ABCC8 A1369S variant and responsiveness to gliclazide, a sulfonylurea [39,40]. Data of the population studies were recently supported by results of the functional analysis of the recombinant KATP channel comprising either the predisposing K23/A1369 or protective E23/ S1369 variants.…”