title: CYP2C9, CYP2C19, ABCB1 genetic polymorphisms and phenytoin plasma concentrations in Mexican-Mestizo patients with epilepsy.
abstract: We aimed to explore the possible influence of CYP2C9 (*2, *3 and IVS8-109 A>T), CYP2C19 (*2, *3 and *17) and ABCB1 (1236C>T, 2677G>A/T and 3435C>T) on phenytoin (PHT) plasma concentrations in 64 Mexican Mestizo (MM) patients with epilepsy currently treated with PHT in mono- (n=25) and polytherapy (n=39). Genotype and allele frequencies of these variants were also estimated in 300 MM healthy volunteers. Linear regression models were used to assess associations between the dependent variables (PHT plasma concentration and dose-corrected PHT concentration) with independent variables (CYP2C9, CYP2C19 and ABCB1 genotypes, ABCB1 haplotypes, age, sex, weight, and polytherapy). In multivariate models, CYP2C9 IVS8-109 T was significantly associated with higher PHT plasma concentrations (t(64)=2.27; P=0.03). Moreover, this allele was more frequent in the supratherapeutic group as compared with the subtherapeutic group (0.13 versus 0.03, respectively; P=0.05, Fisher's exact test). Results suggest that CYP2C9 IVS8-109 T allele may decrease CYP2C9 enzymatic activity on PHT. More research is needed to confirm findings.
authors.affiliation: Doctorate in Biological and Health Sciences, Metropolitan Autonomous University, Campus Xochimilco, Mexico City, Mexico.
authors.forename: A
authors.initials: A
authors.lastname: Ortega-Vázquez
authors.affiliation: Department of Medical and Surgical Therapeutics, University of Extremadura, Campus Plasencia, Plasencia, Spain.|CICAB Clinical Research Centre, Extremadura University Hospital and Medical School Servicio Extremeño de Salud, Badajoz, Spain.
authors.forename: P
authors.initials: P
authors.lastname: Dorado
authors.affiliation: Doctorate in Biological and Health Sciences, Metropolitan Autonomous University, Campus Xochimilco, Mexico City, Mexico.
authors.forename: I
authors.initials: I
authors.lastname: Fricke-Galindo
authors.affiliation: Department of Pharmacy, Chemistry Faculty, National Autonomous University of Mexico and Department of Neuropharmacology, National Institute of Neurology and Neurosurgery Manuel Velasco Suárez, Mexico City, Mexico.
authors.forename: H
authors.initials: H
authors.lastname: Jung-Cook
authors.affiliation: Department of Neurogenetics and Molecular Biology, National Institute of Neurology and Neurosurgery Manuel Velasco Suárez, Mexico City, Mexico.
authors.forename: N
authors.initials: N
authors.lastname: Monroy-Jaramillo
authors.affiliation: Epilepsy Clinic, National Institute of Neurology and Neurosurgery Manuel Velasco Suárez, Mexico City, Mexico.
authors.forename: I E
authors.initials: IE
authors.lastname: Martínez-Juárez
authors.affiliation: Department of Psychiatry, Michigan State University, Lansing, Michigan, USA.
authors.forename: I
authors.initials: I
authors.lastname: Familiar-López
authors.affiliation: CICAB Clinical Research Centre, Extremadura University Hospital and Medical School Servicio Extremeño de Salud, Badajoz, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Peñas-Lledó
authors.affiliation: CICAB Clinical Research Centre, Extremadura University Hospital and Medical School Servicio Extremeño de Salud, Badajoz, Spain.
authors.forename: A
authors.initials: A
authors.lastname: LLerena
authors.affiliation: Department of Biological Systems, Metropolitan Autonomous University, Campus Xochimilco, Mexico City, Mexico.
authors.forename: M
authors.initials: M
authors.lastname: López-López
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D000368:Aged; D000927:Anticonvulsants / Q000008:administration & dosage / Q000097:blood*; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D065731:Cytochrome P-450 CYP2C19 / Q000235:genetics* / Q000378:metabolism; D065729:Cytochrome P-450 CYP2C9 / Q000235:genetics* / Q000378:metabolism; D016903:Drug Monitoring; D004827:Epilepsy / Q000097:blood / Q000188:drug therapy* / Q000208:ethnology / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D016014:Linear Models; D008297:Male; D008800:Mexico / Q000453:epidemiology; D008875:Middle Aged; D015999:Multivariate Analysis; D000071184:Pharmacogenomic Variants / Q000235:genetics*; D010641:Phenotype; D010672:Phenytoin / Q000008:administration & dosage / Q000097:blood*; D012307:Risk Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D000927:Anticonvulsants; D010672:Phenytoin; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19