ABCB1 C3435T Genetic Polymorphism and Response to Glibenclamide Therapy in Patients with Type 2 Diabetes Mellitus

Surendiran A; Pradhan SC; Subrahmanyam DKS; Aparna Agrawal; Umamaheswaran G; Rajan S; Adithan C

Abstract

International Journal of Pharmacology and Clinical Sciences,2015,4,2,12-15.

DOI:10.5530/ijpcs.4.2.1

Published:June 2015

Type:Original Article

Authors:

Author(s) affiliations:

Surendiran A^1*, Pradhan SC1, Subrahmanyam DKS², Aparna Agrawal², Umamaheswaran G¹, Rajan S¹, Adithan C³

¹Department of Pharmacology, JIPMER, Puducherry, India.

²Department of Medicine, JIPMER, Puducherry, India.

³Department of Clinical Pharmacology, JIPMER, Puducherry, India.

Abstract:

Background: Glibenclamide is a substrate and an inhibitor of P-glycoprotein which is coded by the gene ABCB1. Objective: To study the influence of ABCB1 C3435T gene polymorphism on the therapeutic effect of glibenclamide, its plasma levels and hypoglycemic adverse effects. Materials and Methods: The study was done in Type 2 diabetes mellitus patients of South India (n=80) who were on treatment with glibenclamide as a single agent or along with metformin. From a venous blood sample, ABCB1 C3435T genetic polymorphism and plasma levels of glibenclamide were determined. The parameters were compared between genotype groups. Patient characteristics across genotypes were analyzed using one way ANOVA and the association between glycemic status and genotype was studied using Chi Square test. The association between genotypes and parameters such as C/D values, hypoglycemic episodes were compared using Kruskal Wallis Test. Results:There were no significant differences in age, body mass index and duration of treatment between the genotype groups ABCB1 CC, CT and TT. There was no significant association between glycemic status of type 2 diabetes and presence of variant genotypes ABCB1 CT and TT. There were no statistically significant differences in plasma concentration of glibenclamide, number and severity of adverse effects between the genotype groups. Conclusion: ABCB1 C3435T genetic polymorphism did not produce any significant influence on the therapeutic response to glibenclamide, plasma glibenclamide levels and the occurrence of adverse events in South Indian patients with type 2 diabetes mellitus