Metabolic control in type 2 diabetes is associated with sulfonylurea receptor-1 (SUR-1) but not with KCNJ11 polymorphisms

Abstract

Background ----- The sulfonylureas are hypoglycemic agents used for promotion of insulin secretion in type 2 diabetics. They bind to sulfonylurea receptor-1 (SUR-1), which is a functional subunit of the ATP-sensitive potassium channel (KATP). The other component of potassium channel is Kir6.2, encoded by gene KCNJ11. Polymorphisms in these genes may lead to modulated response to sulfonylurea therapy. Aim ----- Aim of this study was to determine a relationship between SUR-1 [exon 16 (-3C/T), exon 31 (Arg1273Arg; AGG→AGA) and exon 33 (S1369A)] and KCNJ11 (E23K) polymorphisms and following parameters of metabolic control in type 2 diabetes: fasting plasma glucose (FPG), postprandial glucose (PPG) and HbA1c in Caucasian type 2 diabetics of the European origin. Methods ----- A total of 228 unrelated patients with type 2 diabetes on sulfonylurea therapy were included in the study. Genotyping of all polymorphisms was performed by PCR-RFLP method; biochemical parameters were determined using standard laboratory methods. Results ----- There was no difference in FPG and PPG concentration in any of the genotype subgroups. However, diabetics with wild type C/C genotype of the SUR-1 exon 16 polymorphism had significantly lower HbA1c concentration compared to the patients with variant T/T genotype [6.9 (6.2-7.7) mmol/L vs. 8.1 (6.7-8.8) mmol/L; p = 0.009]. Also, patients with wild type G/G genotype of the SUR-1 exon 31 polymorphism had significantly higher HbA1c concentration compared to the patients with variant A/A genotype [7.8 (6.9-8.8) mmol/L vs. 6.3 (5.7-6.8) mmol/L; p < 0.001]. Conclusion ----- SUR-1 exon 16 and exon 31 polymorphisms are significantly associated with HbA1c concentration