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

Danese, E; Raimondi, S; Montagnana, M; Tagetti, A; Langaee, T; Borgiani, P; Ciccacci, C; Carcas, AJ; Borobia, AM; Tong, HY; Dávila-Fajardo, C; Rodrigues Botton, M; Bourgeois, S; Deloukas, P; Caldwell, MD; Burmester, JK; Berg, RL; Cavallari, LH; Drozda, K; Huang, M; Zhao, L; Cen, H; Gonzalez-Conejero, R; Roldan, V; Nakamura, Y; Mushiroda, T; Gong, IY; Kim, RB; Hirai, K; Itoh, K; Isaza, C; Beltrán, L; Jiménez-Varo, E; Cañadas-Garre, M; Giontella, A; Kringen, MK; Haug, KBF; Gwak, HS; Lee, KE; Minuz, P; Lee, MTM; Lubitz, SA; Scott, S; Mazzaccara, C; Sacchetti, L; Genç, E; Özer, M; Pathare, A; Krishnamoorthy, R; Paldi, A; Siguret, V; Loriot, M; Kutala, VK; Suarez-Kurtz, G; Perini, J; Denny, JC; Ramirez, AH; Mittal, B; Rathore, SS; Sagreiya, H; Altman, R; Shahin, MHA; Khalifa, SI; Limdi, NA; Rivers, C; Shendre, A; Dillon, C; Suriapranata, IM; Zhou, H; Tan, S; Tatarunas, V; Lesauskaite, V; Zhang, Y; Maitland-van der Zee, AH; Verhoef, TI; de Boer, A; Taljaard, M; Zambon, CF; Pengo, V; Zhang, JE; Pirmohamed, M; Johnson, JA; Fava, C

doi:10.1002/cpt.1323

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.

Danese, E., Raimondi, S., Montagnana, M., Tagetti, A., Langaee, T., Borgiani, P., et al. (2019). Effect of CYP4F2, VKORC1, and CYP2C9 in Influencing Coumarin Dose: A Single-Patient Data Meta-Analysis in More Than 15,000 Individuals. CLINICAL PHARMACOLOGY & THERAPEUTICS, 105(6), 1477-1491-1491 [10.1002/cpt.1323].

Tipologia:	Articolo su rivista
Citazione:	Danese, E., Raimondi, S., Montagnana, M., Tagetti, A., Langaee, T., Borgiani, P., et al. (2019). Effect of CYP4F2, VKORC1, and CYP2C9 in Influencing Coumarin Dose: A Single-Patient Data Meta-Analysis in More Than 15,000 Individuals. CLINICAL PHARMACOLOGY & THERAPEUTICS, 105(6), 1477-1491-1491 [10.1002/cpt.1323].
Lingua:	English
Settore Scientifico Disciplinare:	Settore MED/03 - Genetica Medica
Revisione (peer review):	Esperti anonimi
Tipo:	Articolo
Rilevanza:	Rilevanza internazionale
Digital Object Identifier (DOI):	http://dx.doi.org/10.1002/cpt.1323
Stato di pubblicazione:	Pubblicato
Data di pubblicazione:	giu-2019
Titolo:	Effect of CYP4F2, VKORC1, and CYP2C9 in Influencing Coumarin Dose: A Single-Patient Data Meta-Analysis in More Than 15,000 Individuals
Autori:	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 mostra contributor esterni nascondi contributor esterni
Autori:	Danese, E; Raimondi, S; Montagnana, M; Tagetti, A; Langaee, T; Borgiani, P; Ciccacci, C; Carcas, Aj; Borobia, Am; Tong, Hy; Dávila-Fajardo, C; Rodrigues Botton, M; Bourgeois, S; Deloukas, P; Caldwell, Md; Burmester, Jk; Berg, Rl; Cavallari, Lh; Drozda, K; Huang, M; Zhao, L; Cen, H; Gonzalez-Conejero, R; Roldan, V; Nakamura, Y; Mushiroda, T; Gong, Iy; Kim, Rb; Hirai, K; Itoh, K; Isaza, C; Beltrán, L; Jiménez-Varo, E; Cañadas-Garre, M; Giontella, A; Kringen, Mk; Haug, Kbf; Gwak, Hs; Lee, Ke; Minuz, P; Lee, Mtm; Lubitz, Sa; Scott, S; Mazzaccara, C; Sacchetti, L; Genç, E; Özer, M; Pathare, A; Krishnamoorthy, R; Paldi, A; Siguret, V; Loriot, M; Kutala, Vk; Suarez-Kurtz, G; Perini, J; Denny, Jc; Ramirez, Ah; Mittal, B; Rathore, Ss; Sagreiya, H; Altman, R; Shahin, Mha; Khalifa, Si; Limdi, Na; Rivers, C; Shendre, A; Dillon, C; Suriapranata, Im; Zhou, H; Tan, S; Tatarunas, V; Lesauskaite, V; Zhang, Y; Maitland-van der Zee, Ah; Verhoef, Ti; de Boer, A; Taljaard, M; Zambon, Cf; Pengo, V; Zhang, Je; Pirmohamed, M; Johnson, Ja; Fava, C
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