CYP2C9, CYP2C19, ABCB1 genetic polymorphisms and phenytoin plasma concentrations in Mexican-Mestizo patients with epilepsy
Por:
Ortega-Vazquez, A., Dorado, P., Fricke-Galindo, I., Jung-Cook, H., Monroy-Jaramillo, N., Martinez-Juarez, I. E., Familiar-Lopez, I., Penas-Lledo, E., LLerena, A., Lopez-Lopez, M.
Publicada:
1 jun 2016
Resumen:
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. © 2016 Macmillan Publishers Limited.
Filiaciones:
Ortega-Vazquez, A.:
Metropolitan Autonomous Univ, Doctorate Biol & Hlth Sci, Campus Xochimilco, Mexico City, DF, Mexico
Dorado, P.:
Univ Extremadura, Dept Med & Surg Therapeut, Campus Plasencia, Plasencia, Spain
Extremadura Univ Hosp, CICAB Clin Res Ctr, Badajoz, Spain
Med Sch Servicio Extremeno Salud, Badajoz, Spain
Fricke-Galindo, I.:
Metropolitan Autonomous Univ, Doctorate Biol & Hlth Sci, Campus Xochimilco, Mexico City, DF, Mexico
Jung-Cook, H.:
Univ Nacl Autonoma Mexico, Dept Pharm, Mexico City 04510, DF, Mexico
Natl Inst Neurol & Neurosurg Manuel Velasco Suare, Dept Neuropharmacol, Mexico City, DF, Mexico
Monroy-Jaramillo, N.:
Natl Inst Neurol & Neurosurg Manuel Velasco Suare, Dept Neurogenet & Mol Biol, Mexico City, DF, Mexico
Martinez-Juarez, I. E.:
Natl Inst Neurol & Neurosurg Manuel Velasco Suare, Epilepsy Clin, Mexico City, DF, Mexico
Familiar-Lopez, I.:
Michigan State Univ, Dept Psychiat, Lansing, MI USA
Penas-Lledo, E.:
Extremadura Univ Hosp, CICAB Clin Res Ctr, Badajoz, Spain
Med Sch Servicio Extremeno Salud, Badajoz, Spain
LLerena, A.:
Extremadura Univ Hosp, CICAB Clin Res Ctr, Badajoz, Spain
Med Sch Servicio Extremeno Salud, Badajoz, Spain
Lopez-Lopez, M.:
Metropolitan Autonomous Univ, Dept Biol Syst, Campus Xochimilco,Calzada Hueso 1100, Mexico City 04960, DF, Mexico
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