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

• Published in: Therapeutic advances in endocrinology and metabolism Vol. 2; no. 4; pp. 155 - 164
• Main Authors: El-sisi, Alaa E., Hegazy, Sahar K., Metwally, Shereen S., Wafa, Alaa M., Dawood, Naglaa A.
• Format: Journal Article
• Language: English
• Published: London, England SAGE Publications 01-08-2011; SAGE Publishing
• Subjects: Original Research; Kir6.2; KCNJ11; Arg972 IRS-1 variant; IRS-1; E23K polymorphism; sulfonylurea failure
• ISSN: 2042-0188; 2042-0196
• DOI: 10.1177/2042018811415985

Objective: This study investigated the possibility that genetic factors, such as polymorphism of K inward rectifier subunit (Kir6.2), E23K, and Arg972 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 A1c ≥ 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 Arg972 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 Arg972 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 Arg972 IRS-1 variants are associated with increased risk for secondary failure to sulfonylurea.