title: Associations between MDR1 C3435T polymorphism and drug-resistant epilepsy in the Polish population.
abstract: Epilepsy is a common neurological disorder. About one-third of epileptic patients demonstrate multidrug resistance (MDR) phenotype and develop drug-resistant epilepsy (DRE). Single nucleotide polymorphism (SNP) C3435T (rs1045642), identified in the MDR1 gene, is associated with an increased intestinal expression of P-glycoprotein (P-gp) which affects the levels of anti-epileptic drugs in plasma. The reported study was designed to explore associations between the MDR1-C3435T gene SNP and the risk of DRE in the Polish population. The C3435T polymorphism of MDR1 gene was investigated by the PCR-RFLP technique in 74 patients with DRE and 70 age- and sex-matched non-DRE controls. Blood samples were obtained from patients with drug-resistant epilepsy, treated at the Department of Neurological Surgery, Medical University in Warsaw between the years 2011 and 2012. Odds ratios (ORs) and 95 % confidence intervals (CIs) were calculated for each genotype and allele. Genotype distribution of C3435T polymorphism of MDR1 gene was compared between the DRE patients and controls with significant differences (p < 0.05) between the two investigated groups. A possible association was observed between DRE and the presence of 3435C allele. The 3435C allele was found in 69 % of DRE cases and in 48 % of the used controls. The variant 3435T allele of MDR1 decreased the risk of drug-resistant epilepsy [odds ratio (OR) 0.41; 95 % confidence interval (CI) 0.26-0.67]. The results indicate that the C3435T polymorphism of MDR1 gene may be associated with the incidence of DRE observed in the Polish population.
authors.affiliation: Department of Neurology, Regional Hospital. Dr. Charles Jonscher, Lodz, Poland.
authors.forename: Dominik
authors.initials: D
authors.lastname: Skalski
authors.affiliation: Department of Neurology, TriMedic Medical Center, Lodz, Poland.
authors.forename: Janusz
authors.initials: J
authors.lastname: Wendorff
authors.affiliation: Department of Clinical Pathomorphology, Polish Mother's Memorial Hospital-Research Institute, Lodz, Poland.
authors.forename: Hanna
authors.initials: H
authors.lastname: Romanowicz
authors.affiliation: Department of Neurological Surgery, Medical University, Warsaw, Poland.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Rysz
authors.affiliation: Department of Neurological Surgery, Medical University, Warsaw, Poland.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Marchel
authors.affiliation: Department of Neurology, Polish Mother's Memorial Hospital-Research Institute, Lodz, Poland.
authors.forename: Mariusz
authors.initials: M
authors.lastname: Stasiołek
authors.affiliation: Laboratory of Cancer Genetics, Department of Clinical Pathomorphology, Polish Mother's Memorial Hospital-Research Institute, Rzgowska 281/289, 93-338, Lodz, Poland. smolbea@wp.pl.
authors.forename: Beata
authors.initials: B
authors.lastname: Smolarz
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics; D000328:Adult; D018432:Drug Resistance, Multiple / Q000235:genetics*; D004827:Epilepsy / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008297:Male; D016017:Odds Ratio; D011044:Poland; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D055815:Young Adult
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B
keywords: Drug-resistant epilepsy; MDR1; Polymorphism