Effect of genetic polymorphisms on the development of secondary failure to sulfonylurea in Egyptian patients with type 2 diabetes

Objective: This study investigated the possibility that genetic factors, such as polymorphism of K inward rectifier subunit (Kir6.2), E23K, and Arg 972 polymorphism of insulin receptor substrate-1 (IRS-1), may predispose patients to sulfonylurea failure. Methods: A total of 100 unrelated Egyptian patients with type 2 diabetes were recruited. They were divided into two equal groups: group I consisted of patients with secondary failure to sulfonylurea (hemoglobin A 1c ≥ 8% despite sulfonylurea therapy) while group II consisted of patients whose condition was controlled with oral therapy. Results: Of all the patients, 45% and 14% were carriers of the K allele and Arg 972 variants respectively. The frequency of the K allele was 34% among patients with diabetes that was controlled with oral therapy and 56% among patients with secondary failure to sulfonylurea. The frequency of the Arg 972 IRS-1 variant was 6% among patients with diabetes controlled with oral therapy and 22% among patients with secondary failure. Conclusion: The E23K variant of the Kir6.2 gene and Arg 972 IRS-1 variants are associated with increased risk for secondary failure to sulfonylurea