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...
- 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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Repositorio EdocUR - U. Rosario |
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|
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 |
dc.type.coarversion.fl_str_mv |
http://purl.org/coar/version/c_970fb48d4fbd8a85 |
dc.type.coar.fl_str_mv |
http://purl.org/coar/resource_type/c_6501 |
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 |
dc.relation.uri.spa.fl_str_mv |
https://www.scopus.com/inward/record.uri?eid=2-s2.0-85062731227&doi=10.2147%2fPGPM.S170515&partnerID=40&md5=0253fc4eaab333b4f8aa344f5eb57b77 |
dc.rights.coar.fl_str_mv |
http://purl.org/coar/access_right/c_abf2 |
dc.rights.acceso.spa.fl_str_mv |
Abierto (Texto Completo) |
rights_invalid_str_mv |
Abierto (Texto Completo) http://purl.org/coar/access_right/c_abf2 |
dc.format.mimetype.none.fl_str_mv |
application/pdf |
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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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 |