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.
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; 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. - In: CLINICAL PHARMACOLOGY & THERAPEUTICS. - ISSN 0009-9236. - 105:6(2019), pp. 1477-1491. [10.1002/cpt.1323]
Effect of CYP4F2, VKORC1, and CYP2C9 in Influencing Coumarin Dose: A Single-Patient Data Meta-Analysis in More Than 15,000 Individuals
Mazzaccara, Cristina;Sacchetti, Lucia;
2019
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.File | Dimensione | Formato | |
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Descrizione: Effect of CYP4F2, VKORC1, and CYP2C9 in Influencing Coumarin Dose: A Single-Patient Data Meta-Analysis in More Than 15,000 Individuals
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