title: Lack of association of ABCB1 and PXR polymorphisms with response to treatment in epilepsy.
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.
authors.affiliation: Pharmacogenomics Laboratory, Department of Pharmacology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia. batoolsadat@yahoo.com
authors.forename: B S
authors.initials: BS
authors.lastname: Haerian
authors.forename: K S
authors.initials: KS
authors.lastname: Lim
authors.forename: E H M
authors.initials: EH
authors.lastname: Mohamed
authors.forename: H J
authors.initials: HJ
authors.lastname: Tan
authors.forename: C T
authors.initials: CT
authors.lastname: Tan
authors.forename: A A
authors.initials: AA
authors.lastname: Raymond
authors.forename: C P
authors.initials: CP
authors.lastname: Wong
authors.forename: S W
authors.initials: SW
authors.lastname: Wong
authors.forename: Z
authors.initials: Z
authors.lastname: Mohamed
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D000927:Anticonvulsants / Q000627:therapeutic use; D044466:Asian People / Q000208:ethnology / Q000235:genetics*; D002220:Carbamazepine / Q000627:therapeutic use; D002648:Child; D004827:Epilepsy / Q000188:drug therapy / Q000208:ethnology / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies / Q000379:methods; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D000077297:Pregnane X Receptor; D011987:Receptors, Steroid / Q000235:genetics*; D016896:Treatment Outcome; D014635:Valproic Acid / Q000627:therapeutic use; D044465:White People / Q000208:ethnology / Q000235:genetics*; D055815:Young Adult
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000927:Anticonvulsants; D000077297:Pregnane X Receptor; D011987:Receptors, Steroid; D002220:Carbamazepine; D014635:Valproic Acid