Lack of association between ABCC2 gene variants and treatment response in epilepsy

Aim: The aim of this study was to replicate a previously reported association between drug resistance in epilepsy patients and the 24C > T variant of the ABCC2 gene that codes for the drug efflux transporter MRP2. Patients & methods: We genotyped 381 Caucasian epileptic patients (337 drug resistant and 44 drug responsive) and 247 healthy controls for the ABCC2 gene -24C > T polymorphism (rs717620) and two other nearby SNPs in linkage disequilibrium (1249G > A and 3972C > T). Genotype, allele and three-SNP-haplotype frequencies were compared between groups. Patients were further stratified into four groups according to their degree of drug resistance (as measured by seizure frequency under medication) to perform regression analysis against genotypes and haplotpyes. Results: We detected no significant differences in the distribution of any of the tested alleles, genotypes or haplotypes between the investigated groups. Neither was there an association between genotypes or haplotypes and degree of drug resistance. This study was adequately powered to detect genotype relative risks of above two. Conclusion: Although adequately powered to detect the previously reported effect size and although our definition of drug resistance, following the International League Against Epilepsy guidelines, was slightly stricter than in the original study, we failed to confirm an association between the 24C > T variant in the ABCC2 gene and drug resistance in epilepsy. Original submitted: 31 May 2011; Revision submitted: 15 August 2011