Pharmacogenetic studies with oral anticoagulants. Genome-wide association studies in vitamin K antagonist and direct oral anticoagulants
Cullell, Natalia (Fundació per la Recerca Biomèdica i Social Mútua de Terrassa)
Carrera, Caty (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Muiño, Elena (Fundació per la Recerca Biomèdica i Social Mútua de Terrassa)
Torres, Nuria (Fundació per la Recerca Biomèdica i Social Mútua de Terrassa)
Krupinski, Jerzy (School of Healthcare Science, Manchester Metropolitan University, Manchester, United Kingdom)
Fernandez-Cadenas, Israel (Institut d'Investigació Biomèdica Sant Pau)
Universitat Autònoma de Barcelona

Data:	2018
Resum:	Oral anticoagulants (OAs) are the recommended drugs to prevent cardiovascular events and recurrence in patients with atrial fibrillation (AF) and cardioembolic stroke. We conducted a literature search to review the current state of OAs pharmacogenomics, focusing on Genome Wide Association Studies (GWAs) in patients treated with vitamin K antagonists (VKAs) and direct oral anticoagulants (DOACs). VKAs: Warfarin, acenocoumarol, fluindione and phenprocoumon have long been used, but their interindividual variability and narrow therapeutic/safety ratio makes their dosage difficult. GWAs have been useful in finding genetic variants associated with VKAs response. The main genes involved in VKAs pharmacogenetics are: VKORC1, CYP2C19 and CYP4F2. Variants in these genes have been included in pharmacogenetic algorithms to predict the VKAs dose individually in each patient depending on their genotype and clinical variables. DOACs: Dabigatran, apixaban, rivaroxaban and edoxaban have been approved for patients with AF. They have stable pharmacokinetics and do not require routine blood checks, thus avoiding most of the drawbacks of VKAs. Except for a GWAs performed in patients treated with dabigatran, there is no Genome Wide pharmacogenomics data for DOACs. Pharmacogenomics could be useful to predict the better clinical response and avoid adverse events in patients treated with anticoagulants, identifying the most appropriate anticoagulant drug for each patient. Current pharmacogenomics data show that the polymorphisms affecting VKAs or DOACs are different, concluding that personalized medicine based on pharmacogenomics could be possible. However, more studies are required to implement personalized medicine in clinical practice with OA and based on pharmacogenetics of DOACs.
Ajuts:	Instituto de Salud Carlos III PI15-01978
Nota:	Altres ajuts: This work was supported by Boeringher Ingelheim funding (SEDMAN Project).
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	VKA ; DOACs ; Pharmacogenetics ; GWAs ; Genetics
Publicat a:	Oncotarget, Vol. 9 (june 2018) , p. 29238-29258, ISSN 1949-2553

DOI: 10.18632/oncotarget.25579
PMID: 30018749

21 p, 2.1 MB

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