Association of a variant in exon 31 of the sulfonylurea receptor 1 (SUR1) gene with type 2 diabetes mellitus in French Caucasians

Abstract

The sulfonylurea receptor (SUR1) of the pancreatic beta-cell ATP-sensitive potassium channel plays a key role in glucose-induced insulin secretion. The A-allele of a single nucleotide polymorphism (SNP) in exon 31 of the SUR1 gene (AGG-->AGA; Arg1273Arg) has previously been shown to be associated with hyperinsulinemia in nondiabetic Mexican-American subjects. Here, we have investigated the association of this SNP with type 2 diabetes mellitus (T2DM) in French Caucasian subjects. We have observed an increased frequency of the A allele (37.1% vs 27.6%, P=0.0048; odds ratio 1.54), of the AA genotype (15.7% vs 9.8%; P=0.025), and of the combined AA/AG genotypes (58.5% vs 45.5%, P=0.0098; odds ratio 1.69) in patients compared with controls. This association is stronger in the subgroup of patients with age of diagnosis of diabetes equal to or less than 45 years: A allele 43.2% (P=0.0003 compared with controls; odds ratio 1.99), AA genotype 21.4% (P=0.0032), and combined AA/AG genotypes 65.1% (P=0.0022; odds ratio 2.23). Unexpectedly, the G allele is strongly associated with arterial hypertension in obese diabetic subjects (GG vs AA odds ratio 19.97). In conclusion, we have observed an association of an SNP in exon 31 of the SUR1 gene with T2DM. These data reinforce the hypothesis that insulin secretion defects in T2DM might be at least partially related to allelic variations in the SUR1 gene.