The Impact of CYP2C9 Rs1057910 and rs1799853 Polymorphism on the Effectiveness of Glibenclamide in T2DM Iraqi Patients

Abstract

Background: Diabetes mellitus (DM) is a complex metabolic disorder characterized by chronic hyperglycemia and dysregulation of carbohydrate, lipid, and protein metabolism. Glibenclamide remains one of the most commonly prescribed sulfonylureas for the management of type 2 diabetes mellitus (T2DM). However, interindividual variability in therapeutic response has been widely reported. Genetic polymorphisms, particularly in genes regulating glibenclamide pharmacokinetics and pharmacodynamics, are thought to contribute to these differences in drug disposition and clinical efficacy. Objective: This study aimed to evaluate the impact of CYP2C9 gene polymorphisms on the therapeutic effectiveness of glibenclamide in Iraqi patients with T2DM Iraqi patients. Materials and Methods: A case–control study was conducted in Karbala City, located in central Iraq. The study population comprised 120 patients with a confirmed diagnosis of diabetes mellitus and 100 healthy individuals. Venous blood samples were obtained from all participants for the assessment of glycemic control parameters and for genetic analysis. Sample collection and clinical data acquisition were performed during patients’ routine visits to the Imam Hassan Center for Endocrinology and Diabetes in Karbala City. Results: The findings of this study demonstrated no statistically significant association between CYP2C9 gene polymorphisms (rs1057910 and rs1799853) and therapeutic response to glibenclamide (p ≥ 0.05). However, a statistically significant association was observed between patients’ glycemic response to glibenclamide therapy and gender across both wild-type and mutant genotype groups (p ≤ 0.05). Conclusion: This study highlights important concerns regarding the role of gender (male/female) in the variation of T2DM patients’ response to glibenclamide therapy.