Association of sulfonylurea receptor gene polymorphisms and Type 2 diabetes
sulfonylurea receptor gene, Type 2 diabetes
The sulfonylureas are antidiabetic agents which bind to sulfonylurea receptor-1 (SUR-1) resulting in increase of insulin secretion. (SUR1) gene encodes the SUR1 protein that plays a vital role in glucose-induced insulin secretion. Polymorphisms in this gene have been associated with development of type 2 diabetes mellitus (T2DM) in many populations and may result in response modulation to sulfonylurea therapy. Aim: The purpose of this study was to assess the influence of SUR-1 genetic polymorphisms (SUR 1 exon 16 (-3C/T, cag GCC-tag GCC), SUR-1 exon 31 (Arg1273Arg AGG-AGA), and (SUR-1 exon 33 (S1369A)) on the genetic predisposition to T2DM and to investigate whether these genetic variants may modulate the response to sulfonylurea in Egyptian T2DM patients as assessed by glycated hemoglobin levels (HbA1C). Methods: A total of 86 unrelated patients with T2DM who were receiving sulfonylurea therapy along with 46 healthy control volunteers were enrolled in the study. Genotyping of SUR-1 was performed by polymerase chain reaction restriction fragmentlength polymorphism (PCR-RFLP) method. Results: The present study observed that heterozygote genotype (T/G) of exon 33 was highly expressed in diabetic patients compared to control group (P‹0.001). While the wild type of exons 31 (G/G) and exon 33 (T/T) were significantly higher in controls compared to T2DM patients (P=0.003 and ‹ 0.001 respectively). Conclusion: On the basis of these data; presence of the wild type in SUR 1 exon 31 and 33 may have protective effect against T2DM, whereas presence of heterozygous condition at the same exons may confer susceptibility.