title: Lack of association between polymorphism in ABCC2 gene and response to antiepileptic drug treatment in Croatian patients with epilepsy.
abstract: Despite advances in antiepileptic drug (AED) therapy, about one-third of patients with epilepsy are resistant to drug treatment. Functional impact of polymorphisms in drug-efflux transporter genes may contribute to multidrug resistance theory. Studies on ABCB1 gene gave contradictory results and available data suggest that this polymorphism may not directly cause altered P-glycoprotein (Pgp) transport activity but may be associated with one or more causal variants in the stretch of linkage disequilibrium or is caused by multiple gene polymorphisms. Genetic polymorphisms also occur frequently in other transmembrane transport systems including the multidrug resistance proteins (MRPs, ABCC2). The aim of this research was to investigate the possible association of ABCC2 gene polymorphisms G1249A in exon 10 and C24T in exon 1 with the development of drug resistance. This cross-sectional study is a part of ongoing pharmacogenomic study of epilepsy in Croatian population. All patients enrolled in the study had an established diagnosis of partial complex epilepsy with or without secondary generalization with non lesional brain MRI with epilepsy protocol and have been suffering for more than two years. They were divided into two groups. The first group comprised 52 patients refractory to the current therapy, while the second group consisted of 45 patients with well-controlled seizures. Our data did not identify any significant association between genetic polymorphisms of exon 1 (24C > T) and exon 10 (1249G < A) of ABCC2 gene or any combined effect in response to AED treatment and development of drug resistance in patients with partial complex epilepsy. Statistical significant difference was not found in genotype based analysis, allele frequency, haplotype and combined genotype analysis.
authors.affiliation: University of Zagreb, Dubrava University Hospital, Department of Neurology, Zagreb, Croatia. davor.sporis@kbd.hr
authors.forename: Davor
authors.initials: D
authors.lastname: Sporis
authors.forename: Nada
authors.initials: N
authors.lastname: Bozina
authors.forename: Silvio
authors.initials: S
authors.lastname: Basić
authors.forename: Mila
authors.initials: M
authors.lastname: Lovrić
authors.forename: Tomislav
authors.initials: T
authors.lastname: Babić
authors.forename: Ivana
authors.initials: I
authors.lastname: Susak
authors.forename: Ivana
authors.initials: I
authors.lastname: Marković
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D000927:Anticonvulsants / Q000627:therapeutic use*; D017523:Croatia; D003430:Cross-Sectional Studies; D018432:Drug Resistance, Multiple; D004827:Epilepsy / Q000188:drug therapy* / Q000235:genetics*; D017029:Epilepsy, Complex Partial / Q000235:genetics* / Q000473:pathology; D005091:Exons; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics* / Q000502:physiology; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic; D055815:Young Adult
chemical_list: D000927:Anticonvulsants; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins; C000715087:ABCC2 protein, human