Creating and validating a warfarin pharmacogenetic dosing algorithm for colombian patients

Purpose: 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...

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Autores:
Tipo de recurso:
Fecha de publicación:
2018
Institución:
Universidad del Rosario
Repositorio:
Repositorio EdocUR - U. Rosario
Idioma:
eng
OAI Identifier:
oai:repository.urosario.edu.co:10336/22796
Acceso en línea:
https://doi.org/10.2147/PGPM.S170515
https://repository.urosario.edu.co/handle/10336/22796
Palabra clave:
Alanine
Cysteine
Cytochrome p450 2c9
Glycine
Threonine
Warfarin
Adult
Aged
Algorithm
Amino acid substitution
Article
Cohort analysis
Colombian
Controlled study
Cyp2c9 gene
Cyp4f2 gene
Female
Gene
Genetic polymorphism
Genetic variability
Genotype
Human
Maintenance drug dose
Major clinical study
Male
Multiple linear regression analysis
Pharmacogenetics
Thromboembolism
Very elderly
Vkorc1 gene
Adverse drug reaction
Anticoagulants
Gene frequency
Genetic polymorphism
Rights
License
Abierto (Texto Completo)
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network_name_str Repositorio EdocUR - U. Rosario
repository_id_str
dc.title.spa.fl_str_mv Creating and validating a warfarin pharmacogenetic dosing algorithm for colombian patients
title Creating and validating a warfarin pharmacogenetic dosing algorithm for colombian patients
spellingShingle Creating and validating a warfarin pharmacogenetic dosing algorithm for colombian patients
Alanine
Cysteine
Cytochrome p450 2c9
Glycine
Threonine
Warfarin
Adult
Aged
Algorithm
Amino acid substitution
Article
Cohort analysis
Colombian
Controlled study
Cyp2c9 gene
Cyp4f2 gene
Female
Gene
Genetic polymorphism
Genetic variability
Genotype
Human
Maintenance drug dose
Major clinical study
Male
Multiple linear regression analysis
Pharmacogenetics
Thromboembolism
Very elderly
Vkorc1 gene
Adverse drug reaction
Anticoagulants
Gene frequency
Genetic polymorphism
title_short Creating and validating a warfarin pharmacogenetic dosing algorithm for colombian patients
title_full Creating and validating a warfarin pharmacogenetic dosing algorithm for colombian patients
title_fullStr Creating and validating a warfarin pharmacogenetic dosing algorithm for colombian patients
title_full_unstemmed Creating and validating a warfarin pharmacogenetic dosing algorithm for colombian patients
title_sort Creating and validating a warfarin pharmacogenetic dosing algorithm for colombian patients
dc.subject.keyword.spa.fl_str_mv Alanine
Cysteine
Cytochrome p450 2c9
Glycine
Threonine
Warfarin
Adult
Aged
Algorithm
Amino acid substitution
Article
Cohort analysis
Colombian
Controlled study
Cyp2c9 gene
Cyp4f2 gene
Female
Gene
Genetic polymorphism
Genetic variability
Genotype
Human
Maintenance drug dose
Major clinical study
Male
Multiple linear regression analysis
Pharmacogenetics
Thromboembolism
Very elderly
Vkorc1 gene
Adverse drug reaction
Anticoagulants
Gene frequency
Genetic polymorphism
topic Alanine
Cysteine
Cytochrome p450 2c9
Glycine
Threonine
Warfarin
Adult
Aged
Algorithm
Amino acid substitution
Article
Cohort analysis
Colombian
Controlled study
Cyp2c9 gene
Cyp4f2 gene
Female
Gene
Genetic polymorphism
Genetic variability
Genotype
Human
Maintenance drug dose
Major clinical study
Male
Multiple linear regression analysis
Pharmacogenetics
Thromboembolism
Very elderly
Vkorc1 gene
Adverse drug reaction
Anticoagulants
Gene frequency
Genetic polymorphism
description Purpose: 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.
publishDate 2018
dc.date.created.spa.fl_str_mv 2018
dc.date.accessioned.none.fl_str_mv 2020-05-25T23:58:04Z
dc.date.available.none.fl_str_mv 2020-05-25T23:58:04Z
dc.type.eng.fl_str_mv article
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dc.type.spa.spa.fl_str_mv Artículo
dc.identifier.doi.none.fl_str_mv https://doi.org/10.2147/PGPM.S170515
dc.identifier.issn.none.fl_str_mv 11787066
dc.identifier.uri.none.fl_str_mv https://repository.urosario.edu.co/handle/10336/22796
url https://doi.org/10.2147/PGPM.S170515
https://repository.urosario.edu.co/handle/10336/22796
identifier_str_mv 11787066
dc.language.iso.spa.fl_str_mv eng
language eng
dc.relation.citationEndPage.none.fl_str_mv 178
dc.relation.citationStartPage.none.fl_str_mv 169
dc.relation.citationTitle.none.fl_str_mv Pharmacogenomics and Personalized Medicine
dc.relation.citationVolume.none.fl_str_mv Vol. 11
dc.relation.ispartof.spa.fl_str_mv Pharmacogenomics and Personalized Medicine, ISSN:11787066, Vol.11,(2018); pp. 169-178
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dc.publisher.spa.fl_str_mv Dove Medical Press Ltd
institution Universidad del Rosario
dc.source.instname.spa.fl_str_mv instname:Universidad del Rosario
dc.source.reponame.spa.fl_str_mv reponame:Repositorio Institucional EdocUR
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spelling 05be2068-882c-4b73-8a37-71a88beffefa-1c05a6131-dbf4-48d9-aad3-2dbc0d5da1da-19813f343-876e-415f-b11e-401af04e1e1a-131597829-da17-4345-8b04-f6f021a34740-1e142df44-3ff8-424c-a054-7f7745b4de64-179782770-1193318196002360597260079733068600520948256002020-05-25T23:58:04Z2020-05-25T23:58:04Z2018Purpose: 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.application/pdfhttps://doi.org/10.2147/PGPM.S17051511787066https://repository.urosario.edu.co/handle/10336/22796engDove Medical Press Ltd178169Pharmacogenomics and Personalized MedicineVol. 11Pharmacogenomics and Personalized Medicine, ISSN:11787066, Vol.11,(2018); pp. 169-178https://www.scopus.com/inward/record.uri?eid=2-s2.0-85062731227&doi=10.2147%2fPGPM.S170515&partnerID=40&md5=0253fc4eaab333b4f8aa344f5eb57b77Abierto (Texto Completo)http://purl.org/coar/access_right/c_abf2instname:Universidad del Rosarioreponame:Repositorio Institucional EdocURAlanineCysteineCytochrome p450 2c9GlycineThreonineWarfarinAdultAgedAlgorithmAmino acid substitutionArticleCohort analysisColombianControlled studyCyp2c9 geneCyp4f2 geneFemaleGeneGenetic polymorphismGenetic variabilityGenotypeHumanMaintenance drug doseMajor clinical studyMaleMultiple linear regression analysisPharmacogeneticsThromboembolismVery elderlyVkorc1 geneAdverse drug reactionAnticoagulantsGene frequencyGenetic polymorphismCreating and validating a warfarin pharmacogenetic dosing algorithm for colombian patientsarticleArtículohttp://purl.org/coar/version/c_970fb48d4fbd8a85http://purl.org/coar/resource_type/c_6501Galvez, Jubby MarcelaAlvarado, ClaraPeña, NidiaCifuentes, Ricardo ADuarte, DanielaLaissue, PaulRestrepo Fernández, Carlos MartínContreras Bravo, Nora ConstanzaCalderón Ospina, Carlos AlbertoFonseca Mendoza, Dora JanethORIGINALpgpm-170515-creating-and-validating-a-warfarin-pharmacogenetic-dosing-al-101318.pdfapplication/pdf512065https://repository.urosario.edu.co/bitstreams/9752f01b-193b-43d8-9e24-bc8e72f8d26c/download94e34b237a9ace41139756df476594ddMD51TEXTpgpm-170515-creating-and-validating-a-warfarin-pharmacogenetic-dosing-al-101318.pdf.txtpgpm-170515-creating-and-validating-a-warfarin-pharmacogenetic-dosing-al-101318.pdf.txtExtracted texttext/plain55737https://repository.urosario.edu.co/bitstreams/bf215db0-05cb-48b9-b001-a5bc0bdda069/downloadfa208998f4d16370ca1bda9bee4dfc2eMD52THUMBNAILpgpm-170515-creating-and-validating-a-warfarin-pharmacogenetic-dosing-al-101318.pdf.jpgpgpm-170515-creating-and-validating-a-warfarin-pharmacogenetic-dosing-al-101318.pdf.jpgGenerated Thumbnailimage/jpeg4616https://repository.urosario.edu.co/bitstreams/18cc9cd5-94f4-4274-b7d6-ea7247bb9d5b/downloada2c54fb1672058a4dbfbc4652952baa4MD5310336/22796oai:repository.urosario.edu.co:10336/227962022-05-02 07:37:20.597123https://repository.urosario.edu.coRepositorio institucional EdocURedocur@urosario.edu.co