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Functionally Significant Coumarin-Related Variant Alleles and Time to Therapeutic Range in Chilean Cardiovascular Patients
- Source :
- Clinical and Applied Thrombosis/Hemostasis, Vol 26 (2020), Clinical and Applied Thrombosis/Hemostasis
- Publication Year :
- 2020
- Publisher :
- SAGE Publishing, 2020.
-
Abstract
- 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
- Subjects :
- 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
Subjects
Details
- Language :
- English
- ISSN :
- 19382723
- Volume :
- 26
- Database :
- OpenAIRE
- Journal :
- Clinical and Applied Thrombosis/Hemostasis
- Accession number :
- edsair.doi.dedup.....801ea53e5bbd8ad2be4d3acf2f80b738