Impact of sulfonylurea receptor 1 genetic variability on non-insulin-dependent diabetes mellitus prevalence and treatment: A population study

The high affinity sulfonylurea receptor 1 (SUR1) is involved in the metabol ism of glucose in pancreatic beta -cells, We investigated the impact of the SUR1 intron 16-3t -->c polymorphism on non-insulin-dependent diabetes mell itus (NIDDM) prevalence in a large representative sample of French men and women, 35-64 years old, and explored potential relationships between the SU R1 intron 16 -t -->c polymorphism and sulfonylurea therapy efficiency. This study took place in Lille (northern), Strasbourg (eastern), and Toulouse ( southern France). One hundred and twenty-two subjects with NIDDM were regis tered. We stratified NIDDM subjects according to their medical treatment: s ulfonylureas (n = 70) versus other treatments (n = 50), From the three popu lations, a control group was selected (n = 1,250), Subjects carrying the cc intron 16 genotype had an increased risk of NIDDM [odds ratio (OR) = 1.76, 95% confidence interval (CI) 1.10-2.80; P = 0.017], Subjects bearing at le ast one -3c allele and treated with sulfonylurea agents had fasting plasma triglyceride concentrations 35% lower than subjects that were tt homozygous (P = 0.026), whereas no difference could be detected between genotypes in NIDDM subjects treated with other treatments. The SUR1 intron 16 -3t -->c p olymorphism was associated with an increased susceptibility to NIDDM in thi s population study, and seems to modulate the sulfonylurea therapy efficien cy on hypertriglyceridemia reduction. This observation may help to better t arget the various therapies available for treatment of NIDDM, (C) 2001 Wile y-Liss, Inc.