The common C49620T polymorphism in the sulfonylurea receptor gene (ABCC8), pancreatic beta cell function and long-term diabetic complications in obese patients with long-lasting type 2 diabetes mellitus

Exp Clin Endocrinol Diabetes. 2007 May;115(5):317-21. doi: 10.1055/s-2007-967086.

Abstract

Hypothesis: A gene polymorphism associated with accelerated beta-cell failure may lead to a more rapid development of long-term complications of type 2 diabetes (T2DM) due to a worse metabolic control of the disease.

Aim of the study: Evaluation of an association between the intronic C49620T (exon 16 -3c-->t) polymorphism in the ABCC8 (SUR1) gene and beta-cell function, as well as the prevalence of long-term diabetic complications in obese patients with long-lasting type 2 diabetes.

Methods: Two hundred and fifteen obese patients with at least a 10-year history of T2DM were thoroughly characterized clinically. In all the patients the intravenous glucagon test was performed and the C49620T ABCC8 polymorphism was assessed. Subgroups of patients, classified either according to genotype or to allele carriage, were compared.

Results: No difference was found between the groups in variables describing beta-cell function and the prevalence of chronic diabetic complications, with the exception of a significantly lower incidence of brain stroke in CC homozygotes than in patients carrying T allele (CT+TT). Body mass index was higher in patients carrying C allele than in TT homozygotes. HDL-cholesterol was higher in CT heterozygous than in homozygous CC or TT patients.

Conclusions: There is no association between the ABCC8 polymorphism gene and the beta-cell function or the prevalence of chronic diabetic complications in obese patients with long-term T2DM, except for brain stroke. The results might suggest that the homozygous CC subjects are at lower risk of the complication, but additional studies are warranted to test this finding.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP-Binding Cassette Transporters / genetics*
  • Aged
  • Chronic Disease
  • Diabetes Complications / epidemiology
  • Diabetes Mellitus, Type 2 / complications*
  • Diabetes Mellitus, Type 2 / genetics
  • Diabetes Mellitus, Type 2 / physiopathology
  • Female
  • Glucagon / administration & dosage
  • Humans
  • Injections, Intravenous
  • Insulin Resistance / genetics
  • Insulin-Secreting Cells / physiology*
  • Male
  • Middle Aged
  • Obesity / complications*
  • Obesity / genetics
  • Obesity / physiopathology
  • Polymorphism, Single Nucleotide*
  • Potassium Channels / genetics*
  • Potassium Channels, Inwardly Rectifying / genetics*
  • Prevalence
  • Receptors, Drug / genetics*
  • Stroke / epidemiology
  • Stroke / genetics
  • Sulfonylurea Receptors
  • Time Factors

Substances

  • ABCC8 protein, human
  • ATP-Binding Cassette Transporters
  • Potassium Channels
  • Potassium Channels, Inwardly Rectifying
  • Receptors, Drug
  • Sulfonylurea Receptors
  • Glucagon