engleski

Variants in sulfonylurea receptor-1 gene are associated with type 2 diabetes mellitus in patients on sulfonylurea therapy

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) located in pancreatic beta cells in islets of Langerhans. The other component of potassium channel is Kir6.2, inwardly rectifying ion channel forming a pore, encoded by gene KCNJ11. Numerous polymorphisms of these genes are reported in association with susceptibility to type 2 diabetes and diabetic phenotypes. Aim of this study was to determine a relationship between sulfonylurea receptor-1 (SUR-1) [exon 16 (-3C/T), exon 31 (Arg1273Arg) and exon 33 (S1369A)] and KCNJ11 (E23K) polymorphisms and parameters associated with type 2 diabetes: fasting plasma glucose (FPG), postprandial glucose (PPG) and HbA1c in Caucasian type 2 diabetics. Genotyping of all polymorphisms was preformed by PCR-RFLP method ; biochemical parameters were determined using standard laboratory methods. 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: We have found significant associations of SUR-1 exon 16 and exon 31 polymorphisms with short-term diabetic outcomes, namely HbA1c concentration.

polymorphism; sulfonylurea receptor-1; HbA1c; fasting plasma glucose

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