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Possible Genetic Determinants of Response to Phenytoin in a Group of Colombian Patients With Epilepsy.

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dc.creatorCalderón Ospina, Carlos Alberto
dc.creatorGalvez, Jubby Marcelaspa
dc.creatorLopez-Cabra, Claudiaspa
dc.creatorMorales, Nataliaspa
dc.creatorRestrepo Fernández, Carlos Martín
dc.creatorRodriguez, Jesusspa
dc.creatorAristizabal-Gutierrez, Fabio Ancizarspa
dc.creatorVélez van Meerbeke, Alberto Franciscospa
dc.creatorLaissue, Paulspa
dc.creatorFonseca Mendoza, Dora Janeth
dc.date.accessioned2020-06-11T13:21:54Z
dc.date.available2020-06-11T13:21:54Z
dc.date.created2020spa
dc.description.abstractBackground: Epilepsy is a serious health problem worldwide. Despite the introduction of new antiepileptic drugs (AEDs) almost 30% of these patients have drug-resistant forms of the disease (DRE), with a significant increase in morbi-mortality.Objective: Our objective was to assess the impact of some genetic factors and its possible association with treatment response and adverse drug reactions (ADRs) to phenytoin in 67 adult Colombian patients with epilepsy.Methods: We conducted an analytical, observational, prospective cohort study to screen four polymorphisms in pharmacogenes: CYP2C9*2-c.430C>T (rs1799853), CYP2C9*3-c.1075A>C (rs1057910), ABCB1-c.3435T>C (rs1045642), and SCN1A-IVS5-91G>A (rs3812718), and their association with treatment response. Patients were followed for 1 year to confirm the existence of DRE (non-response) and ADRs using an active pharmacovigilance approach, followed by a consensus in order to classify ADRs according to causality, preventability, intensity and their relation with phenytoin dose, the duration of treatment, and susceptibility factors (DoTS methodology).Results: A little more than half of evaluated subjects (52.2%) were non-responding to phenytoin. Regarding the genotype-phenotype correlation there was no association between polymorphisms of SCN1A and ABCB1 and DRE (non-response) (p = 0.34), and neither with CYP2C9 polymorphisms and the occurrence of ADRs (p = 0.42). We only found an association between polymorphic alleles of CYP2C9 and vestibular-cerebellar ADRs (dizziness, ataxia, diplopia, and dysarthria) (p = 0.001). Alleles CYP2C9*2-c.430C>T and CYP2C9*3-c.1075A>C were identified as susceptibility factors to ADRs in 24% of patients.Conclusions: Decreased function alleles of CYP2C9 were highly predictive of vestibular-cerebellar ADRs to phenytoin in our study (p = 0.001). However, the genetic variants CYP2C9*2-c.430C>T, CYP2C9*3-c.1075A>C, ABCB1-c.3435T>C, and SCN1A-IVS5-91G>A, were not associated with treatment response in our study.eng
dc.format.mimetypeapplication/pdf
dc.identifier.doihttps://doi.org/10.3389/fphar.2020.00555
dc.identifier.issn1663-9812
dc.identifier.urihttps://repository.urosario.edu.co/handle/10336/24946
dc.language.isoeng
dc.publisherFrontiers Media S.A.spa
dc.relation.citationEndPage555
dc.relation.citationStartPage555
dc.relation.citationTitleFrontiers in pharmacology
dc.relation.citationVolumeVol. 11
dc.relation.ispartofFrontiers in pharmacology, ISSN:1663-9812, Vol.11, (2020); pp. 555-555spa
dc.rights.accesRightsinfo:eu-repo/semantics/openAccess
dc.rights.accesoAbierto (Texto Completo)spa
dc.source.instnameinstname:Universidad del Rosariospa
dc.source.reponamereponame:Repositorio Institucional EdocURspa
dc.subject.keyworddrug resistant epilepsyspa
dc.subject.keyworddrug-related side effects and adverse reactionsspa
dc.subject.keywordpharmacogeneticsspa
dc.subject.keywordpharmacovigilancespa
dc.subject.keywordphenytoinspa
dc.titlePossible Genetic Determinants of Response to Phenytoin in a Group of Colombian Patients With Epilepsy.spa
dc.typearticleeng
dc.type.hasVersioninfo:eu-repo/semantics/publishedVersion
dc.type.spaArtículospa
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