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Effect of CYP4F2, VKORC1, and CYP2C9 in Influencing Coumarin Dose: A Single-Patient Data Meta-Analysis in More Than 15,000 Individuals

Title
Effect of CYP4F2, VKORC1, and CYP2C9 in Influencing Coumarin Dose: A Single-Patient Data Meta-Analysis in More Than 15,000 Individuals
Authors
Danese, ElisaRaimondi, SaraMontagnana, MartinaTagetti, AngelaLangaee, TaimourBorgiani, PaolaCiccacci, CinziaCarcas, Antonio J.Borobia, Alberto M.Tong, Hoi Y.Davila-Fajardo, CristinaBotton, Mariana RodriguesBourgeois, StephaneDeloukas, PanosCaldwell, Michael D.Burmester, Jim K.Berg, Richard L.Cavallari, Larisa H.Drozda, KatarzynaHuang, MinZhao, Li-ZiCen, Han-JingGonzalez-Conejero, RocioRoldan, VanessaNakamura, YusukeMushiroda, TaiseiGong, Inna Y.Kim, Richard B.Hirai, KeitaItoh, KunihikoIsaza, CarlosBeltran, LeonardoJimenez-Varo, EnriqueCanadas-Garre, MarisaGiontella, AliceKringen, Marianne K.Haug, Kari Bente FossGwak, Hye SunLee, Kyung EunMinuz, PietroLee, Ming Ta MichaelLubitz, Steven A.Scott, StuartMazzaccara, CristinaSacchetti, LuciaGenc, EceOzer, MahmutPathare, AnilKrishnamoorthy, RajagopalPaldi, AndrasSiguret, VirginieLoriot, Marie-AnneKutala, Vijay KumarSuarez-Kurtz, GuilhermePerini, JamilaDenny, Josh C.Ramirez, Andrea H.Mittal, BalrajRathore, Saurabh SinghSagreiya, HershAltman, RussShahin, Mohamed Hossam A.Khalifa, Sherief, ILimdi, Nita A.Rivers, CharlesShendre, AditiDillon, ChrislySuriapranata, Ivet M.Zhou, Hong-HaoTan, Sheng-LanTatarunas, VacisLesauskaite, VaivaZhang, YumaoMaitland-van der Zee, Anke H.Verhoef, Talitha, Ide Boer, AnthoniusTaljaard, MonicaZambon, Carlo FedericoPengo, VittorioZhang, Jieying EunicePirmohamed, MunirJohnson, Julie A.Fava, Cristiano
Ewha Authors
곽혜선
SCOPUS Author ID
곽혜선scopus
Issue Date
2019
Journal Title
CLINICAL PHARMACOLOGY & THERAPEUTICS
ISSN
0009-9236JCR Link

1532-6535JCR Link
Citation
CLINICAL PHARMACOLOGY & THERAPEUTICS vol. 105, no. 6, pp. 1477 - 1491
Publisher
WILEY
Indexed
SCI; SCIE; SCOPUS WOS scopus
Document Type
Article
Abstract
The cytochrome P450 (CYP)4F2 gene is known to influence mean coumarin dose. The aim of the present study was to undertake a meta-analysis at the 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 of 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% confidence interval (CI) 7-10%), with a higher effect in women, in patients taking acenocoumarol, and in white patients. 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.
DOI
10.1002/cpt.1323
Appears in Collections:
약학대학 > 약학과 > Journal papers
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