title: Absence of a general association between ABCB1 genetic variants and response to antiepileptic drugs in epilepsy patients.
abstract: Over-expression of efflux transporter P-glycoprotein (PgP) encoded by ABCB1 gene has been implicated in poor responsive epilepsy. Several genetic variants have been shown to influence the expression levels of P-glycoprotein. The aim of the present study was to investigate the role of ABCB1 polymorphisms: C1236T, G2677T/A and C3435T in determining drug response to first line antiepileptic drugs (AEDs) namely phenobarbitone, phenytoin, carbamazepine and valproate in North Indian cohort of epilepsy patients. DNA samples were obtained from 392 consecutive epilepsy patients, out of which 228 had completed follow-up evaluation at 12 months. After attaining steady state of the AEDs in the first two months of study, 133 patients showed complete freedom from seizures (no-seizure group) and 95 patients continued to have seizures (recurrent-seizures group) in the remaining period of study. Comparison of "no-seizure" and "recurrent-seizures" groups revealed no significant differences in allelic, genotypic and haplotypic frequencies for all the studied variants. In conclusion, our finding disproves a general association between ABCB1 polymorphisms and drug response in epilepsy patients.
authors.affiliation: Institute of Genomics and Integrative Biology (IGIB), Council of Scientific and Industrial Research (CSIR), Mall Road, Delhi 110 007, India.
authors.forename: Sandeep
authors.initials: S
authors.lastname: Grover
authors.forename: Kiran
authors.initials: K
authors.lastname: Bala
authors.forename: Sangeeta
authors.initials: S
authors.lastname: Sharma
authors.forename: M
authors.initials: M
authors.lastname: Gourie-Devi
authors.forename: Ruchi
authors.initials: R
authors.lastname: Baghel
authors.forename: Harpreet
authors.initials: H
authors.lastname: Kaur
authors.forename: Meenal
authors.initials: M
authors.lastname: Gupta
authors.forename: Puneet
authors.initials: P
authors.lastname: Talwar
authors.forename: Ritushree
authors.initials: R
authors.lastname: Kukreti
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*; D002220:Carbamazepine / Q000627:therapeutic use; D004827:Epilepsy / Q000188:drug therapy* / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D010597:Pharmacogenetics; D010634:Phenobarbital / Q000627:therapeutic use; D010672:Phenytoin / Q000627:therapeutic use; D014635:Valproic Acid / Q000627:therapeutic use; 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; D002220:Carbamazepine; D014635:Valproic Acid; D010672:Phenytoin; D010634:Phenobarbital