The effect of CYP4F2, VKORC1 and CYP2C9 in influencing coumarin dose: A single patient data meta-analysis in more than 15,000 individuals



Danese, Elisa, Raimondi, Sara, Montagnana, Martina, Tagetti, Angela, Langaee, Taimour, Borgiani, Paola, Ciccacci, Cinzia, Carcas, Antonio J, Borobia, Alberto M, Tong, Hoi Y
et al (show 73 more authors) (2019) The effect of CYP4F2, VKORC1 and CYP2C9 in influencing coumarin dose: A single patient data meta-analysis in more than 15,000 individuals. Clinical pharmacology and therapeutics, 105 (6). 1477 - 1491.

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Abstract

The CYP4F2 gene is known to influence mean coumarin dose. The aim of the present study was to undertake a meta-analysis at individual patients' level to capture the possible effect of ethnicity, gene-gene interaction or other drugs on the association and to verify if inclusion of CYP4F2*3 variant into dosing algorithms improves the prediction of mean coumarin dose. We asked the authors of our previous meta-analysis (30 articles) and of 38 new articles retrieved by a systematic review to send us individual patients' data. The final collection consists 15,754 patients split into a derivation and validation cohort. The CYP4F2*3 polymorphism was consistently associated with an increase in mean coumarin dose (+9% (95%CI 7-10%), with a higher effect in females, in patients taking acenocoumarol and in Whites. The inclusion of the CYP4F2*3 in dosing algorithms slightly improved the prediction of stable coumarin dose. New pharmacogenetic equations potentially useful for clinical practice were derived. This article is protected by copyright. All rights reserved.

Item Type: Article
Depositing User: Symplectic Admin
Date Deposited: 21 Jan 2019 10:05
Last Modified: 30 Jul 2021 07:31
DOI: 10.1002/cpt.1323
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3031492