title: Pharmacogenetics of adverse reactions to antiepileptic drugs.
abstract: BACKGROUND
  Adverse drug reactions (ADRs) are a major public health concern and a leading cause of morbidity and mortality in the world. In the case of antiepileptic drugs (AEDs), ADRs constitute a barrier to successful treatment since they decrease treatment adherence and impact patients' quality of life of patients. Pharmacogenetics aims to identify genetic polymorphisms associated with drug safety. This article presents a review of genes coding for drug metabolising enzymes and drug transporters, and HLA system genes that have been linked to AED-induced ADRs.
  
  
  METHODS
  To date, several genetic variations associated with drug safety have been reported: CYP2C9*2 and *3 alleles, which code for enzymes with decreased activity, have been linked to phenytoin (PHT)-induced neurotoxicity; GSTM1 null alleles with hepatotoxicity induced by carbamazepine (CBZ) and valproic acid (VPA); EPHX1 polymorphisms with teratogenesis; ABCC2 genetic variations with CBZ- and VPA-induced neurological ADRs; and HLA alleles (e.g. HLA-B*15:02, -A*31:01, -B*15:11, -C*08:01) with cutaneous ADRs.
  
  
  CONCLUSIONS
  Published findings show that there are ADRs with a pharmacogenetic basis and a high interethnic variability, which indicates a need for future studies in different populations to gather more useful results for larger number of patients. The search for biomarkers that would allow predicting ADRs to AEDs could improve pharmacotherapy for epilepsy.
authors.affiliation: Programa de Doctorado en Ciencias Biológicas y de la Salud, Universidad Autónoma Metropolitana, Unidad Xochimilco, Coyoacán, México D.F. , México.
authors.forename: I
authors.initials: I
authors.lastname: Fricke-Galindo
authors.affiliation: Departamento de Neuropsicofarmacología, Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez, Departamento de Farmacia, Universidad Nacional Autónoma de México, Tlalpan, México D.F., México.
authors.forename: H
authors.initials: H
authors.lastname: Jung-Cook
authors.affiliation: CICAB Centro de Investigación Clínica, Complejo Hospitalario Universitario y Facultad de Medicina, Universidad de Extremadura, Servicio Extremeño de Salud, Badajoz, España.
authors.forename: A
authors.initials: A
authors.lastname: LLerena
authors.affiliation: Departamento de Sistemas Biológicos, Universidad Autónoma Metropolitana, Unidad Xochimilco, Coyoacán, México D.F., México. Electronic address: mlopez@correo.xoc.uam.mx.
authors.forename: M
authors.initials: M
authors.lastname: López-López
mesh_terms: D000927:Anticonvulsants / Q000009:adverse effects* / Q000627:therapeutic use; D064420:Drug-Related Side Effects and Adverse Reactions; D004827:Epilepsy / Q000188:drug therapy; D004851:Epoxide Hydrolases / Q000235:genetics; D015235:HLA-B Antigens / Q000235:genetics; D006801:Humans; D000089762:Multidrug Resistance-Associated Protein 2; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic
chemical_list: C000715087:ABCC2 protein, human; D000927:Anticonvulsants; D015235:HLA-B Antigens; D000089762:Multidrug Resistance-Associated Protein 2; D004851:Epoxide Hydrolases; C522330:EPHX1 protein, human
keywords: ABCC2; Adverse drug reactions; Antiepileptic drugs; Antígeno leucocitario humano (HLA); CYP2C9; Farmacogenética; Fármacos antiepilépticos; Human leukocyte antigen (HLA); Pharmacogenetics; Reacciones adversas a medicamentos