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

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

doi:https://doi.org/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

Elisa Danese, Sara Raimondi, Martina Montagnana, Angela Tagetti, Taimour Langaee, Paola Borgiani, Cinzia Ciccacci, Antonio J. Carcas, Alberto M. Borobia, Hoi Y. Tong, Cristina Dávila-Fajardo, Mariana Rodrigues Botton, Stephane Bourgeois, Panos Deloukas, Michael D. Caldwell, Jim K. Burmester, Richard L. Berg, Larisa H. Cavallari, Katarzyna Drozda, Min HuangLi-Zi Zhao, Han-Jing Cen, Rocio Gonzalez-Conejero, Vanessa Roldan, Yusuke Nakamura, Taisei Mushiroda, Inna Y. Gong, Richard B. Kim, Keita Hirai, Kunihiko Itoh, Carlos Isaza, Leonardo Beltrán, Enrique Jiménez-Varo, Marisa Cañadas-Garre, Alice Giontella, Marianne K. Kringen, Kari Bente Foss Haug, Hye Sun Gwak, Kyung Eun Lee, Pietro Minuz, Ming Ta Michael Lee, Steven A. Lubitz, Stuart Scott, Cristina Mazzaccara, Lucia Sacchetti, Ece Genç, Mahmut Özer, Anil Pathare, Rajagopal Krishnamoorthy, Andras Paldi, Virginie Siguret, Marie-Anne Loriot, Vijay Kumar Kutala, Guilherme Suarez-Kurtz, Jamila Perini, Josh C. Denny, Andrea H. Ramirez, Balraj Mittal, Saurabh Singh Rathore, Hersh Sagreiya, Russ Altman, Mohamed Hossam A. Shahin, Sherief I. Khalifa, Nita A. Limdi, Charles Rivers, Aditi Shendre, Chrisly Dillon, Ivet M. Suriapranata, Hong-Hao Zhou, Sheng-Lan Tan, Vacis Tatarunas, Vaiva Lesauskaite, Yumao Zhang, Anke H. Maitland-van der Zee, Talitha I. Verhoef, Anthonius de Boer, Monica Taljaard, Carlo Federico Zambon, Vittorio Pengo, Jieying Eunice Zhang, Munir Pirmohamed, Julie A. Johnson, Cristiano Fava

Research output: Contribution to journal › Article › Academic › peer-review

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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.

Original language	English
Pages (from-to)	1477-1491
Journal	Clinical Pharmacology and Therapeutics
Volume	105
Issue number	6
DOIs	https://doi.org/10.1002/cpt.1323
Publication status	Published - Jun 2019

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Danese, E., Raimondi, S., Montagnana, M., Tagetti, A., Langaee, T., Borgiani, P., Ciccacci, C., Carcas, A. J., Borobia, A. M., Tong, H. Y., Dávila-Fajardo, C., Rodrigues Botton, M., Bourgeois, S., Deloukas, P., Caldwell, M. D., Burmester, J. K., Berg, R. L., Cavallari, L. H., Drozda, K., ... Fava, C. (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 and Therapeutics, 105(6), 1477-1491. https://doi.org/10.1002/cpt.1323

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

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{\textquoteright} 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.",

author = "Elisa Danese and Sara Raimondi and Martina Montagnana and Angela Tagetti and Taimour Langaee and Paola Borgiani and Cinzia Ciccacci and Carcas, {Antonio J.} and Borobia, {Alberto M.} and Tong, {Hoi Y.} and Cristina D{\'a}vila-Fajardo and {Rodrigues Botton}, Mariana and Stephane Bourgeois and Panos Deloukas and Caldwell, {Michael D.} and Burmester, {Jim K.} and Berg, {Richard L.} and Cavallari, {Larisa H.} and Katarzyna Drozda and Min Huang and Li-Zi Zhao and Han-Jing Cen and Rocio Gonzalez-Conejero and Vanessa Roldan and Yusuke Nakamura and Taisei Mushiroda and Gong, {Inna Y.} and Kim, {Richard B.} and Keita Hirai and Kunihiko Itoh and Carlos Isaza and Leonardo Beltr{\'a}n and Enrique Jim{\'e}nez-Varo and Marisa Ca{\~n}adas-Garre and Alice Giontella and Kringen, {Marianne K.} and Haug, {Kari Bente Foss} and Gwak, {Hye Sun} and Lee, {Kyung Eun} and Pietro Minuz and Lee, {Ming Ta Michael} and Lubitz, {Steven A.} and Stuart Scott and Cristina Mazzaccara and Lucia Sacchetti and Ece Gen{\c c} and Mahmut {\"O}zer and Anil Pathare and Rajagopal Krishnamoorthy and Andras Paldi and Virginie Siguret and Marie-Anne Loriot and Kutala, {Vijay Kumar} and Guilherme Suarez-Kurtz and Jamila Perini and Denny, {Josh C.} and Ramirez, {Andrea H.} and Balraj Mittal and Rathore, {Saurabh Singh} and Hersh Sagreiya and Russ Altman and Shahin, {Mohamed Hossam A.} and Khalifa, {Sherief I.} and Limdi, {Nita A.} and Charles Rivers and Aditi Shendre and Chrisly Dillon and Suriapranata, {Ivet M.} and Hong-Hao Zhou and Sheng-Lan Tan and Vacis Tatarunas and Vaiva Lesauskaite and Yumao Zhang and {Maitland-van der Zee}, {Anke H.} and Verhoef, {Talitha I.} and {de Boer}, Anthonius and Monica Taljaard and Zambon, {Carlo Federico} and Vittorio Pengo and Zhang, {Jieying Eunice} and Munir Pirmohamed and Johnson, {Julie A.} and Cristiano Fava",

year = "2019",

month = jun,

doi = "https://doi.org/10.1002/cpt.1323",

language = "English",

volume = "105",

pages = "1477--1491",

journal = "Clinical Pharmacology and Therapeutics",

issn = "0009-9236",

publisher = "Nature Publishing Group",

number = "6",

}

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-Z, Cen, H-J, 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-A, 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-H, Tan, S-L, 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 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 and Therapeutics, vol. 105, no. 6, pp. 1477-1491. https://doi.org/10.1002/cpt.1323

TY - JOUR

T1 - Effect of CYP4F2, VKORC1, and CYP2C9 in Influencing Coumarin Dose: A Single-Patient Data Meta-Analysis in More Than 15,000 Individuals

AU - Danese, Elisa

AU - Raimondi, Sara

AU - Montagnana, Martina

AU - Tagetti, Angela

AU - Langaee, Taimour

AU - Borgiani, Paola

AU - Ciccacci, Cinzia

AU - Carcas, Antonio J.

AU - Borobia, Alberto M.

AU - Tong, Hoi Y.

AU - Dávila-Fajardo, Cristina

AU - Rodrigues Botton, Mariana

AU - Bourgeois, Stephane

AU - Deloukas, Panos

AU - Caldwell, Michael D.

AU - Burmester, Jim K.

AU - Berg, Richard L.

AU - Cavallari, Larisa H.

AU - Drozda, Katarzyna

AU - Huang, Min

AU - Zhao, Li-Zi

AU - Cen, Han-Jing

AU - Gonzalez-Conejero, Rocio

AU - Roldan, Vanessa

AU - Nakamura, Yusuke

AU - Mushiroda, Taisei

AU - Gong, Inna Y.

AU - Kim, Richard B.

AU - Hirai, Keita

AU - Itoh, Kunihiko

AU - Isaza, Carlos

AU - Beltrán, Leonardo

AU - Jiménez-Varo, Enrique

AU - Cañadas-Garre, Marisa

AU - Giontella, Alice

AU - Kringen, Marianne K.

AU - Haug, Kari Bente Foss

AU - Gwak, Hye Sun

AU - Lee, Kyung Eun

AU - Minuz, Pietro

AU - Lee, Ming Ta Michael

AU - Lubitz, Steven A.

AU - Scott, Stuart

AU - Mazzaccara, Cristina

AU - Sacchetti, Lucia

AU - Genç, Ece

AU - Özer, Mahmut

AU - Pathare, Anil

AU - Krishnamoorthy, Rajagopal

AU - Paldi, Andras

AU - Siguret, Virginie

AU - Loriot, Marie-Anne

AU - Kutala, Vijay Kumar

AU - Suarez-Kurtz, Guilherme

AU - Perini, Jamila

AU - Denny, Josh C.

AU - Ramirez, Andrea H.

AU - Mittal, Balraj

AU - Rathore, Saurabh Singh

AU - Sagreiya, Hersh

AU - Altman, Russ

AU - Shahin, Mohamed Hossam A.

AU - Khalifa, Sherief I.

AU - Limdi, Nita A.

AU - Rivers, Charles

AU - Shendre, Aditi

AU - Dillon, Chrisly

AU - Suriapranata, Ivet M.

AU - Zhou, Hong-Hao

AU - Tan, Sheng-Lan

AU - Tatarunas, Vacis

AU - Lesauskaite, Vaiva

AU - Zhang, Yumao

AU - Maitland-van der Zee, Anke H.

AU - Verhoef, Talitha I.

AU - de Boer, Anthonius

AU - Taljaard, Monica

AU - Zambon, Carlo Federico

AU - Pengo, Vittorio

AU - Zhang, Jieying Eunice

AU - Pirmohamed, Munir

AU - Johnson, Julie A.

AU - Fava, Cristiano

PY - 2019/6

Y1 - 2019/6

N2 - 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.

AB - 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.

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UR - https://www.ncbi.nlm.nih.gov/pubmed/30506689

U2 - https://doi.org/10.1002/cpt.1323

DO - https://doi.org/10.1002/cpt.1323

M3 - Article

C2 - 30506689

SN - 0009-9236

VL - 105

SP - 1477

EP - 1491

JO - Clinical Pharmacology and Therapeutics

JF - Clinical Pharmacology and Therapeutics

IS - 6

ER -

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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