Common ABCB1 polymorphisms are not associated with multidrug resistance in epilepsy using a gene-wide tagging approach

Pharmacogenet Genomics. 2007 Mar;17(3):217-20. doi: 10.1097/01.fpc.0000230408.23146.b1.

Abstract

P-glycoprotein, the product of the ABCB1 gene, is a proposed mechanism of pharmacoresistance in epilepsy. Previous attempts to correlate the ABCB1 C3435T SNP, or a three-SNP haplotype containing C3435T with epilepsy pharmacoresistance have produced discordant findings. We analysed these single nucleotide polymorphisms (SNPs), plus a more comprehensive set of tagging SNPs describing common variation in ABCB1 in a case-control study. No significant association of C3435T (P=0.55), the three-SNP haplotype (lowest P=0.14) or any gene-wide tagging SNP (lowest P=0.17) with multidrug resistance in epilepsy was identified. Meta-analysis of studies using the same definition of multidrug resistance (n=1064) also demonstrated no significant association of C3435T with multidrug resistance (P=0.31). These findings suggest that C3435T is unlikely to be a marker for epilepsy multidrug resistance. In addition, no evidence for a role of other common ABCB1 polymorphisms was found using a potentially more powerful gene-wide tagging approach.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B
  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Adult
  • Aged
  • Aged, 80 and over
  • Anticonvulsants / therapeutic use
  • Case-Control Studies
  • Drug Resistance, Multiple / genetics*
  • Epilepsy / drug therapy
  • Epilepsy / genetics*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Molecular Diagnostic Techniques*
  • Multidrug Resistance-Associated Proteins / genetics
  • Organic Anion Transporters / genetics*
  • Polymorphism, Single Nucleotide*

Substances

  • ABCB1 protein, human
  • ATP Binding Cassette Transporter, Subfamily B
  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Anticonvulsants
  • Multidrug Resistance-Associated Proteins
  • Organic Anion Transporters