Lack of association of ABCB1 and PXR polymorphisms with response to treatment in epilepsy

Haerian, B.S. and Lim, K.S. and Mohamed, E.H.M. and Tan, H.J. and Tan, C.T. and Raymond, A.A. and Wong, C.P. and Wong, S.W. and Mohamed, Z. (2011) Lack of association of ABCB1 and PXR polymorphisms with response to treatment in epilepsy. Seizure-European Journal of Epilepsy, 20 (5). pp. 387-394. ISSN 1059-1311

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Abstract

It is proposed that overexpression of P-glycoprotein (P-gp), encoded by the ABC subfamily B member 1 (ABCB1) gene, is involved in resistance to antiepileptic drugs (AEDs) in about 30 of patients with epilepsy. Genetic variation and haplotype patterns are population specific which may cause different phenotypes such as response to AEDs. Although several studies examined the link between the common polymorphisms in the ABCB1 gene with resistance to AEDs, the results have been conflicting. This controversy may be caused by the effect of some confounders such as ethnicity and polytherapy. Moreover, expression of the ABCB1 gene is under the control of pregnane X receptor (PXR). Evidence showed that PXR gene contribute to the response to treatment. The aim of this study was to assess the association of ABCB1 and PXR genetic polymorphisms with response to the carbamazepine (CBZ) or sodium valproate (VPA) monotherapy in epilepsy. Genotypes were assessed in 685 Chinese, Indian, and Malay epilepsy patients for ABCB1 (C1236T, G2677T, C3435T) and PXR (G7635A) polymorphisms. No association between these polymorphisms and their haplotypes, and interaction between them, with response to treatment was observed in the overall group or in the Chinese, Indian, and Malay subgroups. Our data showed that these polymorphisms may not contribute to the response to CBZ or VPA monotherapy treatment in epilepsy. (C) 2011 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Item Type: Article
Additional Information: Haerian, B. S. Lim, K. S. Mohamed, E. H. M. Tan, H. J. Tan, C. T. Raymond, A. A. Wong, C. P. Wong, S. W. Mohamed, Z.
Uncontrolled Keywords: Epilepsy; ABCB1; PXR; Polymorphism; P-glycoprotein; Antiepileptic drug
Subjects: R Medicine
Divisions: Faculty of Medicine
Depositing User: Ms Haslinda Lahuddin
Date Deposited: 14 Mar 2013 07:52
Last Modified: 14 Mar 2013 07:52
URI: http://eprints.um.edu.my/id/eprint/5080

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