Association of Insulin Receptor Substrate 1 Gene Polymorphism (Rs2943640) with Glibenclamide Therapeutic Response in Iraqi Patients with Type 2 Diabetes Mellitus

Abstract

Objective: This study aims to evaluate the association of the insulin receptor substrate 1 (IRS1) rs2943640 single nucleotide polymorphism (SNP) with the effectiveness of glibenclamide therapy in Iraqi diabetic patients treated with glibenclamide. Methods: This cross-sectional study was conducted in Karbala City, located in central Iraq, from September 2024 to December 2025, and enrolled a total of 160 individuals with a confirmed diagnosis of type 2 diabetes mellitus (T2DM). Venous blood samples were obtained from all participants for the genotyping of the rs2943640 (A/C) SNP and assessment of biochemical parameters, including glycemic indices, lipid profiles, and liver and kidney functions. Results: The genotype frequencies of rs2943640 A/C are 30 % for AA, 61.9 % for AC, and 8.1 % for CC. No statistically significant differences between the three patient groups in biochemical parameters, including glycemic indices, lipid profiles, kidney functions, and aspartate aminotransferase (AST), while alanine aminotransferase (ALT) showed a significant difference among the patient groups. Conclusion: Our results show no statistically significant association between IRS1 rs2943640 (A/C) SNP and therapeutic response to glibenclamide in Iraqi T2DM patients.