Metabolic control in type 2 diabetes is associated with sulfonylurea receptor-1 (SUR-1) but not with KCNJ11 polymorphisms.
OBJECTIVE
Sulfonylureas are hypoglycemic agents used for promotion of insulin secretion in type 2 diabetics (T2D). They bind to sulfonylurea receptor-1 (SUR-1), which is a functional subunit of the ATP-sensitive potassium channel (K(ATP)). The other component of the potassium channel is Kir6.2, encoded by gene KCNJ11. Polymorphisms in these genes may lead to modulated response to sulfonylurea therapy. The 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 the following parameters of metabolic control in T2D: fasting plasma glucose (FPG), postprandial glucose (PPG) and HbA1c in Caucasian T2D of European origin.


METHODS
A total of 228 unrelated patients with T2D 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].


CONCLUSIONS
SUR-1 exon 16 and exon 31 polymorphisms are significantly associated with HbA1c concentration.
Nikolac
Nora
N
University Department of Chemistry, Sestre Milosrdnice University Hospital, Zagreb, Croatia. nora.nikolac@gmail.com
Simundic
Ana-Maria
AM
Katalinic
Darko
D
Topic
Elizabeta
E
Cipak
Andrea
A
Zjacic Rotkvic
Vanja
V
D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000368:Aged; D000483:Alleles; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D005091:Exons / Q000235:genetics; D005260:Female; D005838:Genotype; D005947:Glucose / Q000378:metabolism*; D006442:Glycated Hemoglobin / Q000378:metabolism*; D006801:Humans; D008074:Lipoproteins / Q000097:blood; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics*; D011446:Prospective Studies; D011955:Receptors, Drug / Q000235:genetics*; D064233:Sulfonylurea Receptors; D000099161:Kcnj11 Channel
D018528:ATP-Binding Cassette Transporters; D005947:Glucose; D006442:Glycated Hemoglobin; D008074:Lipoproteins; D024661:Potassium Channels, Inwardly Rectifying; D011955:Receptors, Drug; D064233:Sulfonylurea Receptors; D000099161:Kcnj11 Channel; C577507:ABCC8 protein, human