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

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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.

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