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Creating and validating a warfarin pharmacogenetic dosing algorithm for colombian patients

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dc.creatorGalvez, Jubby Marcelaspa
dc.creatorRestrepo Fernández, Carlos Martín
dc.creatorContreras Bravo, Nora Constanza
dc.creatorAlvarado, Claraspa
dc.creatorCalderón Ospina, Carlos Alberto
dc.creatorPeña, Nidiaspa
dc.creatorCifuentes, Ricardo Aspa
dc.creatorDuarte, Danielaspa
dc.creatorLaissue, Paulspa
dc.creatorFonseca Mendoza, Dora Janeth
dc.date.accessioned2020-05-25T23:58:04Z
dc.date.available2020-05-25T23:58:04Z
dc.date.created2018spa
dc.description.abstractPurpose: Warfarin is an oral anticoagulant associated with adverse reaction to drugs due to wide inter-and intra-individual dosage variability. Warfarin dosage has been related to non-genetic and genetic factors. CYP2C9 and VKORC1 gene polymorphisms affect warfarin metabolism and dosage. Due to the central role of populations’ ethnical and genetic origin on warfarin dosage variability, novel algorithms for Latin American subgroups are necessary to establish safe anticoagulation therapy. Patients and methods: We genotyped CYP2C9*2 (c.430C and gt; T), CYP2C9*3 (c.1075A and gt; C), CYP4F2 (c.1297G and gt; A), and VKORC1 (-1639 G and gt; A) polymorphisms in 152 Colombian patients who received warfarin. We evaluated the impact on the variability of patients’ warfarin dose requirements. Multiple linear regression analysis, using genetic and non-genetic variables, was used for creating an algorithm for optimal warfarin maintenance dose. Results: Median weekly prescribed warfarin dosage was significantly lower in patients having the VKORC1-1639 AA genotype and poor CYP2C9*2/*2,*2/*3 metabolizers than their wild-type counterparts. We found a 2.3-fold increase in mean dose for normal sensitivity patients (wild-type VKORC1/CYP2C9 genotypes) compared to the other groups (moderate and high sensitivity); 31.5% of the patients in our study group had warfarin sensitivity-related genotypes. The estimated regression equation accounted for 44.4% of overall variability in regard to warfarin maintenance dose. The algorithm was validated, giving 45.9% correlation (R 2 =0.459). Conclusion: Our results describe and validate the first algorithm for predicting warfarin maintenance in a Colombian mestizo population and have contributed toward the understanding of pharmacogenetics in a Latin American population subgroup. © 2018 Galvez et al.eng
dc.format.mimetypeapplication/pdf
dc.identifier.doihttps://doi.org/10.2147/PGPM.S170515
dc.identifier.issn11787066
dc.identifier.urihttps://repository.urosario.edu.co/handle/10336/22796
dc.language.isoengspa
dc.publisherDove Medical Press Ltdspa
dc.relation.citationEndPage178
dc.relation.citationStartPage169
dc.relation.citationTitlePharmacogenomics and Personalized Medicine
dc.relation.citationVolumeVol. 11
dc.relation.ispartofPharmacogenomics and Personalized Medicine, ISSN:11787066, Vol.11,(2018); pp. 169-178spa
dc.relation.urihttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85062731227&doi=10.2147%2fPGPM.S170515&partnerID=40&md5=0253fc4eaab333b4f8aa344f5eb57b77spa
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.keywordAlaninespa
dc.subject.keywordCysteinespa
dc.subject.keywordCytochrome p450 2c9spa
dc.subject.keywordGlycinespa
dc.subject.keywordThreoninespa
dc.subject.keywordWarfarinspa
dc.subject.keywordAdultspa
dc.subject.keywordAgedspa
dc.subject.keywordAlgorithmspa
dc.subject.keywordAmino acid substitutionspa
dc.subject.keywordArticlespa
dc.subject.keywordCohort analysisspa
dc.subject.keywordColombianspa
dc.subject.keywordControlled studyspa
dc.subject.keywordCyp2c9 genespa
dc.subject.keywordCyp4f2 genespa
dc.subject.keywordFemalespa
dc.subject.keywordGenespa
dc.subject.keywordGenetic polymorphismspa
dc.subject.keywordGenetic variabilityspa
dc.subject.keywordGenotypespa
dc.subject.keywordHumanspa
dc.subject.keywordMaintenance drug dosespa
dc.subject.keywordMajor clinical studyspa
dc.subject.keywordMalespa
dc.subject.keywordMultiple linear regression analysisspa
dc.subject.keywordPharmacogeneticsspa
dc.subject.keywordThromboembolismspa
dc.subject.keywordVery elderlyspa
dc.subject.keywordVkorc1 genespa
dc.subject.keywordAdverse drug reactionspa
dc.subject.keywordAnticoagulantsspa
dc.subject.keywordGene frequencyspa
dc.subject.keywordGenetic polymorphismspa
dc.titleCreating and validating a warfarin pharmacogenetic dosing algorithm for colombian patientsspa
dc.typearticleeng
dc.type.hasVersioninfo:eu-repo/semantics/publishedVersion
dc.type.spaArtículospa
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