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 Kristiansen 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; Andrea H Ramirez; Yumao Zhang; Anke H Maitland-van der Zee; Talitha I Verhoef; Anthonius de Boer

doi: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 Kristiansen 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, Andrea H Ramirez, Yumao Zhang, Anke H Maitland-van der Zee, Talitha I Verhoef, Anthonius de Boer

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

Abstract

The CYP4F2 gene is known to influence mean coumarin dose. The aim of the present study was to undertake a meta-analysis at 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 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%CI 7-10%), with a higher effect in females, in patients taking acenocoumarol and in Whites. 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. This article is protected by copyright. All rights reserved.

Original language	English
Pages (from-to)	1477-1491
Number of pages	14
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_et_al-2019-Clinical_Pharmacology_&_TherapeuticsFinal published version, 374 KBLicence: Taverne

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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., Botton, M. R., Bourgeois, S., Deloukas, P., Caldwell, M. D., Burmester, J. K., Berg, R. L., Cavallari, L. H., Drozda, K., ... de Boer, A. (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 CYP4F2 gene is known to influence mean coumarin dose. The aim of the present study was to undertake a meta-analysis at 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 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%CI 7-10%), with a higher effect in females, in patients taking acenocoumarol and in Whites. 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. This article is protected by copyright. All rights reserved.",

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 Botton, {Mariana Rodrigues} 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 Kristiansen} and {Bente Foss Haug}, Kari 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 Ramirez, {Andrea H} and Yumao Zhang and {Maitland-van der Zee}, {Anke H} and Verhoef, {Talitha I} and {de Boer}, Anthonius",

year = "2019",

month = jun,

doi = "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, Botton, MR, 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, Bente Foss Haug, K, Gwak, HS, Lee, KE, Minuz, P, Lee, MTM, Lubitz, SA, Scott, S, Mazzaccara, C, Sacchetti, L, Ramirez, AH, Zhang, Y, Maitland-van der Zee, AH, Verhoef, TI & de Boer, A 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 - Botton, Mariana Rodrigues

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 Kristiansen

AU - Bente Foss Haug, Kari

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 - Ramirez, Andrea H

AU - Zhang, Yumao

AU - Maitland-van der Zee, Anke H

AU - Verhoef, Talitha I

AU - de Boer, Anthonius

PY - 2019/6

Y1 - 2019/6

N2 - The CYP4F2 gene is known to influence mean coumarin dose. The aim of the present study was to undertake a meta-analysis at 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 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%CI 7-10%), with a higher effect in females, in patients taking acenocoumarol and in Whites. 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. This article is protected by copyright. All rights reserved.

AB - The CYP4F2 gene is known to influence mean coumarin dose. The aim of the present study was to undertake a meta-analysis at 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 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%CI 7-10%), with a higher effect in females, in patients taking acenocoumarol and in Whites. 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. This article is protected by copyright. All rights reserved.

U2 - 10.1002/cpt.1323

DO - 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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