Effect of CYP4F2, VKORC1, and CYP2C9 in Influencing Coumarin Dose: A Single‐Patient Data Meta‐Analysis in More Than 15, 000 Individuals. Issue 6 (17th February 2019)

• Record Type: Journal Article
• Authors: Danese, Elisa; Raimondi, Sara; Montagnana, Martina; Tagetti, Angela; Langaee, Taimour; Borgiani, Paola; Ciccacci, Cinzia; Carcas, Antonio J.; Borobia, Alberto M.; Tong, Hoi Y.; Dávila‐Fajardo, Cristina; Rodrigues Botton, Mariana; Bourgeois, Stephane; Deloukas, Panos; Caldwell, Michael D.; Burmester, Jim K.; Berg, Richard L.; Cavallari, Larisa H.; Drozda, Katarzyna; Huang, Min; Zhao, Li‐Zi; Cen, Han‐Jing; Gonzalez‐Conejero, Rocio; Roldan, Vanessa; Nakamura, Yusuke; Mushiroda, Taisei; Gong, Inna Y.; Kim, Richard B.; Hirai, Keita; Itoh, Kunihiko; Isaza, Carlos; Beltrán, Leonardo; Jiménez‐Varo, Enrique; Cañadas‐Garre, Marisa; Giontella, Alice; Kringen, Marianne K.; Haug, Kari Bente Foss; Gwak, Hye Sun; Lee, Kyung Eun; Minuz, Pietro; Lee, Ming Ta Michael; Lubitz, Steven A.; Scott, Stuart; Mazzaccara, Cristina; Sacchetti, Lucia; Genç, Ece; Özer, Mahmut; Pathare, Anil; Krishnamoorthy, Rajagopal; Paldi, Andras; Siguret, Virginie; Loriot, Marie‐Anne; Kutala, Vijay Kumar; Suarez‐Kurtz, Guilherme; Perini, Jamila; Denny, Josh C.; Ramirez, Andrea H.; Mittal, Balraj; Rathore, Saurabh Singh; Sagreiya, Hersh; Altman, Russ; Shahin, Mohamed Hossam A.; Khalifa, Sherief I.; Limdi, Nita A.; Rivers, Charles; Shendre, Aditi; Dillon, Chrisly; Suriapranata, Ivet M.; Zhou, Hong‐Hao; Tan, Sheng‐Lan; Tatarunas, Vacis; Lesauskaite, Vaiva; Zhang, Yumao; Maitland‐van der Zee, Anke H.; Verhoef, Talitha I.; de Boer, Anthonius; Taljaard, Monica; Zambon, Carlo Federico; Pengo, Vittorio; Zhang, Jieying Eunice; Pirmohamed, Munir; Johnson, Julie A.; Fava, Cristiano;
• Is Part Of: Clinical pharmacology & therapeutics. Volume 105:Issue 6(2019)
• Page Start: 1477
• Page End: 1491
• Publication Date: 2019-02-17
• Subjects: Pharmacology -- Periodicals; Therapeutics -- Periodicals; 615.5
• DOI: 10.1002/cpt.1323
• Languages: English
• ISSNs: 0009-9236

Abstract

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.