title: MDR-1 and MRP2 Gene Polymorphisms in Mexican Epileptic Pediatric Patients with Complex Partial Seizures.
abstract: Although the Pgp efflux transport protein is overexpressed in resected tissue of patients with epilepsy, the presence of polymorphisms in MDR1/ABCB1 and MRP2/ABCC2 in patients with antiepileptic-drugs resistant epilepsy (ADR) is controversial. The aim of this study was to perform an exploratory study to identify nucleotide changes and search new and reported mutations in patients with ADR and patients with good response (CTR) to antiepileptic drugs (AEDs) in a rigorously selected population. We analyzed 22 samples In Material and Methods, from drug-resistant patients with epilepsy and 7 samples from patients with good response to AEDs. Genomic DNA was obtained from leukocytes. Eleven exons in both genes were genotyped. The concentration of drugs in saliva and plasma was determined. The concentration of valproic acid in saliva was lower in ADR than in CRT. In ABCB1, five reported SNPs and five unreported nucleotide changes were identified; rs2229109 (GA) and rs2032582 (AT and AG) were found only in the ADR. Of six SNPs associated with the ABCC2 that were found in the study population, rs3740066 (TT) and 66744T > A (TG) were found only in the ADR. The strongest risk factor in the ABCB1 gene was identified as the TA genotype of rs2032582, whereas for the ABCC2 gene the strongest risk factor was the T allele of rs3740066. The screening of SNPs in ACBC1 and ABCC2 indicates that the Mexican patients with epilepsy in this study display frequently reported ABCC1 polymorphisms; however, in the study subjects with a higher risk factor for drug resistance, new nucleotide changes were found in the ABCC2 gene. Thus, the population of Mexican patients with AED-resistant epilepsy (ADR) used in this study exhibits genetic variability with respect to those reported in other study populations; however, it is necessary to explore this polymorphism in a larger population of patients with ADR.
authors.affiliation: Programa de Biomedicina y Biotecnología Molecular, Escuela Nacional de Ciencias Biológicas del Instituto Politécnico Nacional , Mexico City , Mexico ; Unidad de Investigación Médica en Enfermedades Neurológicas, Hospital de Especialidades, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social , Mexico City , Mexico.
authors.forename: David
authors.initials: D
authors.lastname: Escalante-Santiago
authors.affiliation: Unidad de Investigación Médica en Enfermedades Neurológicas, Hospital de Especialidades, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social , Mexico City , Mexico.
authors.forename: Iris Angélica
authors.initials: IA
authors.lastname: Feria-Romero
authors.affiliation: Programa de Biomedicina y Biotecnología Molecular, Escuela Nacional de Ciencias Biológicas del Instituto Politécnico Nacional , Mexico City , Mexico.
authors.forename: Rosa María
authors.initials: RM
authors.lastname: Ribas-Aparicio
authors.affiliation: Neurología, Hospital de Pediatría, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social , Mexico City , Mexico.
authors.forename: Dario
authors.initials: D
authors.lastname: Rayo-Mares
authors.affiliation: Departamento de Ciencias Farmacéuticas de la Facultad de Química, Universidad de la República , Montevideo , Uruguay.
authors.forename: Pietro
authors.initials: P
authors.lastname: Fagiolino
authors.affiliation: Departamento de Ciencias Farmacéuticas de la Facultad de Química, Universidad de la República , Montevideo , Uruguay.
authors.forename: Marta
authors.initials: M
authors.lastname: Vázquez
authors.affiliation: Instituto Nacional de Salude Publica , Cuernavaca , Mexico.
authors.forename: Consuelo
authors.initials: C
authors.lastname: Escamilla-Núñez
authors.affiliation: Unidad de Investigación Médica en Enfermedades Neurológicas, Hospital de Especialidades, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social , Mexico City , Mexico.
authors.forename: Israel
authors.initials: I
authors.lastname: Grijalva-Otero
authors.affiliation: Unidad de Investigación Médica en Enfermedades Neurológicas, Hospital de Especialidades, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social , Mexico City , Mexico.
authors.forename: Miguel Angel
authors.initials: MA
authors.lastname: López-García
authors.affiliation: Unidad de Investigación Médica en Enfermedades Neurológicas, Hospital de Especialidades, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social , Mexico City , Mexico.
authors.forename: Sandra
authors.initials: S
authors.lastname: Orozco-Suárez
keywords: ABCB1; ABCC2; Mexican patients; drug-resistant; epilepsy; single-nucleotide polymorphisms, anti-epileptic drugs