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 sub-strate-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.