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

Scientific paper - Original scientific paper

• Author: Nora Nikolac
• Author: Ana-Maria Šimundić
• Author: Darko Katalinić
• Author: Elizabeta Topić
• Author: Andrea Čipak
• Author: Vanja Zjačić-Rotkvić
• Author's institution: University of Zagreb; School of Medicine
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Clinical Medical Sciences

Abstract (english)

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.

• Keywords (english): ATP-Binding Cassette Transporters / genetics; Aged; Alleles; Diabetes Mellitus, Type 2 / metabolism; Exons / genetics; Female; Genotype; Glucose / metabolism; Glycated Hemoglobin A / metabolism; Humans; Lipoproteins / blood; Male; Middle Aged; Polymorphism, Genetic; Potassium Channels, Inwardly Rectifying / genetics; Prospective Studies; Receptors, Drug / genetics; Sulfonylurea Receptors
• Language: english
• Publication type: Scientific paper - Original scientific paper
• Publication status: Published
• Peer review: Peer review
• Publication version: Accepted version
• Journal title: Archives of Medical Research
• Numbering: vol. 40, no. 5, pp. 387-392
• p-ISSN: 0188-4409
• DOI: https://doi.org/10.1016/j.arcmed.2009.06.006
• URN:NBN: urn:nbn:hr:105:907447
• Publication: 2009-07
• Document URL: https://doi.org/10.1016/j.arcmed.2009.06.006
• Type of resource: Text
• Access conditions: Open access
• Created on: 2024-03-28 11:26:16