Common ABCB1 polymorphisms are not associated with multidrug resistance in epilepsy using a gene-wide tagging approach.
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.
Leschziner
Guy D
GD
Imperial College London, London, UK.
Andrew
Toby
T
Leach
John Paul
JP
Chadwick
David
D
Coffey
Alison J
AJ
Balding
David J
DJ
Bentley
David R
DR
Pirmohamed
Munir
M
Johnson
Michael R
MR
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000927:Anticonvulsants / Q000627:therapeutic use; D016022:Case-Control Studies; D018432:Drug Resistance, Multiple / Q000235:genetics*; D004827:Epilepsy / Q000188:drug therapy / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D025202:Molecular Diagnostic Techniques; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics; D027361:Organic Anion Transporters / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000927:Anticonvulsants; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D027361:Organic Anion Transporters; C513055:ABCB1 protein, human