Functionally Significant Coumarin-Related Variant Alleles and Time to Therapeutic Range in Chilean Cardiovascular Patients
| Autor: | Gerald Godoy, María A Lavanderos, Patricio Salas, Jessica Muñoz, G. Llull, Daniela Cruz, Francisca Tamayo, Gabriela Bravo, Luis A. Quiñones, Fanny Mejías, Nelson Varela, Mario Rojo, Annabella Arredondo, Gabriel Verón, María Paz Bertoglia, Ángela Roco, Juan Carlos Rubilar, Paulo Véliz, Elena Nieto, Suárez M |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Male
lcsh:Diseases of the circulatory (Cardiovascular) system Time Factors Vitamin K Epoxide Reductase Population CYP2C19 030204 cardiovascular system & hematology Bioinformatics coumarin 03 medical and health sciences 0302 clinical medicine Coumarins Cytochrome P450 2C9 Humans Medicine Chile education Adverse effect CYP2C9 Alleles pharmacogenetics Aged 030304 developmental biology Aged 80 and over 0303 health sciences Acenocoumarol education.field_of_study Polymorphism Genetic acenocoumarol business.industry VKA Warfarin Anticoagulants Hematology General Medicine Middle Aged Cardiovascular Diseases lcsh:RC666-701 Original Article Female VKORC1 polymorphisms business Pharmacogenetics medicine.drug |
| Zdroj: | Clinical and Applied Thrombosis/Hemostasis, Vol 26 (2020) Clinical and Applied Thrombosis/Hemostasis |
| ISSN: | 1938-2723 |
| Popis: | Indexación: Scopus. Despite the development of new oral agents over the last decade, vitamin K antagonists (VKAs) remain the most widely used anticoagulants for treating and preventing thromboembolism worldwide. In Chile, the Ministry of Health indicates that acenocoumarol should be used in preference to any other coumarin. Complications of inappropriate dosing are among the most frequently reported adverse events associated with this medication. It is well known that polymorphisms in pharmacokinetic and pharmacodynamic proteins related to coumarins (especially warfarin) influence response to these drugs. This work analyzed the impact of CYP2C19*2 (rs4244285), CYP1A2*1F (rs762551), GGCx (rs11676382), CYP2C9*2 (rs1799853), CYP2C9*3 (rs1057910), CYP4F2 (rs2108622), VKORC1 (rs9923231), VKORC1 (rs7294), CYP3A4*1B (rs2740574), and ABCB1 (rs1045642) polymorphisms on time to therapeutic range for oral anticoagulants in 304 Chilean patients. CYP2C9*3 polymorphisms were associated with time to therapeutic range for acenocoumarol in Chilean patients, and the CYP4F2 TT genotype, MDR1 A allele, CYP1A2 A allele, and CYP3A4T allele are promising variants that merit further analysis. The presence of polymorphisms explained only 4.1% of time to therapeutic range for acenocoumarol in a multivariate linear model. These results improve our understanding of the basis of ethnic variations in drug metabolism and response to oral anticoagulant therapy. We hope that these findings will contribute to developing an algorithm for VKA dose adjustment in the Chilean population in the near future, decreasing the frequency of stroke, systemic embolism, and bleeding-related adverse events. https://journals.sagepub.com/doi/10.1177/1076029620909154 |
| Databáze: | OpenAIRE |
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