| ORIGINAL ARTICLE
|Year : 2014 | Volume
| Issue : 3 | Page : 265-269
Association of polymorphisms of CYP2C9, CYP2C19, and ABCB1, and activity of P-glycoprotein with response to anti-epileptic drugs
SR Taur1, NB Kulkarni1, PP Gandhe1, BK Thelma2, SH Ravat3, NJ Gogtay1, UM Thatte1
1 Department of Clinical Pharmacology, Seth GS Medical College and KEM Hospital, Mumbai, India
2 Department of Genetics, University of Delhi South Campus, New Delhi, India
3 Department of Neurology, Seth GS Medical College and KEM Hospital, Mumbai, India
Background and Objective: Epilepsy, the most common neurological disorder, has treatment failure rate of 20 to 25%. Inter-individual variability in drug response can be attributed to genetic polymorphism in genes encoding different drug metabolizing enzymes, drug transporters (P-gp), and enzymes involved in sodium channel biosynthesis. The present study attempted to evaluate association of polymorphisms of CYP2C9, CYP2C19, and ABCB1, and P-gp activity with treatment response in patients with epilepsy. Materials and Methods: Patients with epilepsy on phenytoin and/or phenobarbital and/or carbamazepine were categorized into responders and non-responders as per the International League Against Epilepsy. Plasma drug concentration was estimated by high-performance liquid chromatography. P-gp activity was measured by flow cytometry using rhodamine efflux. The polymerase chain reaction (PCR-RFLP) was used to study polymorphisms of ABCB1 (C3435T), CYP2C9 (416 C > T, and 1061 A > T), and CYP2C19 (681 G > A and 636 G > A). Results: Of total 117 patients enrolled in this study, genotype data was available for 115 patients. P-gp activity was higher in non-responders (n = 68) compared to responders (n = 47) (P<0.001). No association of 416 C > T and 1061 A > T in CYP2C9 or 681 G > A and 636 G > A in CYP2C19 was observed with response phenotype in genotypic analysis. Significant genotypic (odds ratio, OR = 4.5; 95% CI, 1.04 to 20.99) and allelic association (OR = 1.73; 95% CI, 1.02 to 2.95) was observed with ABCB1 C3435T and response phenotype. Conclusions: The response to antiepileptics seems to be modulated by C3435T in ABCB1 or P-gp activity. At present, role of other genetic factors in treatment responsiveness in epilepsy appears limited, warranting analysis in a larger cohort.
Dr. N J Gogtay
Department of Clinical Pharmacology, Seth GS Medical College and KEM Hospital, Mumbai
Source of Support: Grants from the Dept. of Biotechnology, Govt. of India,, Conflict of Interest: The corresponding author, Dr. Nithya Gogtay, is the Editor of the Journal of Postgraduate Medicine.
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