title: Lack of association between ABCC2 gene variants and treatment response in epilepsy.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Clinical Neurology, Medical University of Vienna, Vienna, Austria.
authors.forename: Eva
authors.initials: E
authors.lastname: Hilger
authors.forename: Eva Maria
authors.initials: EM
authors.lastname: Reinthaler
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Stogmann
authors.forename: Christoph
authors.initials: C
authors.lastname: Hotzy
authors.forename: Ekaterina
authors.initials: E
authors.lastname: Pataraia
authors.forename: Christoph
authors.initials: C
authors.lastname: Baumgartner
authors.forename: Alexander
authors.initials: A
authors.lastname: Zimprich
authors.forename: Fritz
authors.initials: F
authors.lastname: Zimprich
mesh_terms: D000328:Adult; D000483:Alleles; D054316:Biomarkers, Pharmacological; D004827:Epilepsy / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012640:Seizures / Q000188:drug therapy
chemical_list: D054316:Biomarkers, Pharmacological; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins; C000715087:ABCC2 protein, human