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

B. S. Haerian, K. S. Lim, E. H M Mohamed, Hui Jan Tan, C. T. Tan, Raymond Azman Ali, C. P. Wong, Sau Wei Wong, Z. Mohamed

Research output: Contribution to journalArticle

23 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)387-394
Number of pages8
JournalSeizure
Volume20
Issue number5
DOIs
Publication statusPublished - Jun 2011

Fingerprint

Epilepsy
Anticonvulsants
Carbamazepine
Valproic Acid
Haplotypes
Genes
P-Glycoprotein
Genetic Polymorphisms
Therapeutics
Genotype
Phenotype
pregnane X receptor
Population

Keywords

  • ABCB1
  • Antiepileptic drug
  • Epilepsy
  • P-glycoprotein
  • Polymorphism
  • PXR

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology

Cite this

Lack of association of ABCB1 and PXR polymorphisms with response to treatment in epilepsy. / Haerian, B. S.; Lim, K. S.; Mohamed, E. H M; Tan, Hui Jan; Tan, C. T.; Ali, Raymond Azman; Wong, C. P.; Wong, Sau Wei; Mohamed, Z.

In: Seizure, Vol. 20, No. 5, 06.2011, p. 387-394.

Research output: Contribution to journalArticle

Haerian, B. S. ; Lim, K. S. ; Mohamed, E. H M ; Tan, Hui Jan ; Tan, C. T. ; Ali, Raymond Azman ; Wong, C. P. ; Wong, Sau Wei ; Mohamed, Z. / Lack of association of ABCB1 and PXR polymorphisms with response to treatment in epilepsy. In: Seizure. 2011 ; Vol. 20, No. 5. pp. 387-394.
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