Published on:31st Aug, 2015
International Journal of Pharmacology and Clinical Sciences, 2015; 4(2):12-15
Original Article | doi:10.5530/ijpcs.4.2.1

ABCB1 C3435T genetic Polymorphism and response to Glibenclamide therapy in patients with type 2 diabetes mellitus


Authors and affiliation (s):

Surendiran A1*, Pradhan SC1, Subrahmanyam DKS2, Aparna Agrawal2, Umamaheswaran G1, Rajan S1 and 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. The influence of ABCB1C3435T gene polymorphism on the therapeutic effect of glibenclamide and its plasma levels has not been studied. 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.

Key Words: ABCB1 C3435T, Diabetes Mellitus, Drug Transporters, Glibenclamide, MDR1, Personalized Medicine, Pharmacogenetics.