Absence of a general association between ABCB1 genetic variants and response to antiepileptic drugs in epilepsy patients

Biochimie. 2010 Sep;92(9):1207-12. doi: 10.1016/j.biochi.2010.04.008. Epub 2010 Apr 24.

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.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics*
  • Adolescent
  • Adult
  • Anticonvulsants / therapeutic use*
  • Carbamazepine / therapeutic use
  • Epilepsy / drug therapy*
  • Epilepsy / genetics*
  • Female
  • Genotype
  • Humans
  • Male
  • Pharmacogenetics
  • Phenobarbital / therapeutic use
  • Phenytoin / therapeutic use
  • Valproic Acid / therapeutic use
  • Young Adult

Substances

  • ABCB1 protein, human
  • ATP Binding Cassette Transporter, Subfamily B
  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Anticonvulsants
  • Carbamazepine
  • Valproic Acid
  • Phenytoin
  • Phenobarbital