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 Boer; Monica Taljaard; Carlo Federico Zambon; Vittorio Pengo; Jieying Eunice Zhang; Munir Pirmohamed; Julie A. Johnson; Cristiano Fava

doi:10.1002/cpt.1323

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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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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, …

Clinical pharmacology and therapeutics, Vol.105(6), pp.1477-1491

06/2019

DOI: https://doi.org/10.1002/cpt.1323

PMID: 30506689

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.

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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
Creators - without role: Elisa Danese - University of Verona
Sara Raimondi - University of Verona
Martina Montagnana - University of Verona
Angela Tagetti - University of Verona
Taimour Langaee - University of Florida
Paola Borgiani - University of Rome Tor Vergata
Cinzia Ciccacci - University of Rome Tor Vergata
Antonio J. Carcas - Autonomous University of Madrid
Alberto M. Borobia - Autonomous University of Madrid
Hoi Y. Tong - Autonomous University of Madrid
Cristina Dávila-Fajardo - Instituto de Investigación Biosanitaria de Granada
Mariana Rodrigues Botton - Universidade Federal do Rio Grande do Sul
Stephane Bourgeois - Queen Mary University of London
Panos Deloukas - Queen Mary University of London
Michael D. Caldwell - Marshfield Clinic
Jim K. Burmester - Gundersen Health System
Richard L. Berg - Marshfield Clinic
Larisa H. Cavallari - University of Florida
Katarzyna Drozda - University of Illinois at Chicago
Min Huang - Sun Yat-sen University
Li‐Zi Zhao - Sun Yat‐Sen University
Han‐Jing Cen - Guangzhou Women and Children's Medical Center
Rocio Gonzalez-Conejero - Universidad de Murcia
Vanessa Roldan - Universidad de Murcia
Yusuke Nakamura - RIKEN Center for Integrative Medical Sciences
Taisei Mushiroda - RIKEN Center for Integrative Medical Sciences
Inna Y. Gong - Western University
Richard B. Kim - Western University
Keita Hirai - University of Shizuoka
Kunihiko Itoh - University of Shizuoka
Carlos Isaza - Technological University of Pereira
Leonardo Beltrán - Central University of Valle del Cauca
Enrique Jiménez-Varo - Hospital Universitario Puerta del Mar
Marisa Cañadas-Garre - Queen's University Belfast
Alice Giontella - University of Verona
Marianne K. Kringen - Diakonhjemmet Hospital
Kari Bente Foss Haug - Oslo University Hospital
Hye Sun Gwak - Ewha Womans University
Kyung Eun Lee - Chungbuk National University
Pietro Minuz - University of Verona
Ming Ta Michael Lee - Academia Sinica
Steven A. Lubitz - Massachusetts General Hospital
Stuart Scott - Icahn School of Medicine at Mount Sinai
Cristina Mazzaccara - Ceinge Biotecnologie Avanzate
Lucia Sacchetti - Ceinge Biotecnologie Avanzate
Ece Genç - Yeditepe University
Mahmut Özer - Yeditepe University
Anil Pathare - Sultan Qaboos University
Rajagopal Krishnamoorthy - Inserm
Andras Paldi - École Pratique des Hautes Études
Virginie Siguret - Inserm
Marie‐Anne Loriot - Service de Biochimie UF Pharmacogénétique et Oncologie Moléculaire
Vijay Kumar Kutala - Nizam's Institute of Medical Sciences
Guilherme Suarez-Kurtz - Instituto Nacional do Câncer
Jamila Perini - Universidade Estadual da Zona Oeste
Josh C. Denny - Vanderbilt University
Andrea H. Ramirez - Vanderbilt University
Balraj Mittal - Babasaheb Bhimrao Ambedkar University
Saurabh Singh Rathore - Babasaheb Bhimrao Ambedkar University
Hersh Sagreiya - Stanford University
Russ Altman - Stanford University
Mohamed Hossam A. Shahin - University of Florida
Sherief I. Khalifa - Gulf Medical University
Nita A. Limdi - University of Alabama at Birmingham
Charles Rivers - University of Alabama at Birmingham
Aditi Shendre - Indiana University – Purdue University Indianapolis
Chrisly Dillon - University of Alabama at Birmingham
Ivet M. Suriapranata - Pelita Harapan University
Hong‐Hao Zhou - Central South University
Sheng‐Lan Tan - Central South University
Vacis Tatarunas - Lithuanian University of Health Sciences
Vaiva Lesauskaite - Lithuanian University of Health Sciences
Yumao Zhang - Utrecht University
Anke H. Maitland-van der Zee - University of Amsterdam
Talitha I. Verhoef - University College London
Anthonius Boer - Utrecht University
Monica Taljaard - Ottawa Hospital
Carlo Federico Zambon - University of Padua
Vittorio Pengo - University of Padua
Jieying Eunice Zhang - University of Liverpool
Munir Pirmohamed - University of Liverpool
Julie A. Johnson - University of Florida
Cristiano Fava - University of Verona
Publication Details: Clinical pharmacology and therapeutics, Vol.105(6), pp.1477-1491
Number of pages: 15
Grant note: CARIVERONA Foundation British Heart Foundation (BHF) (RG/14/5/30893)
Identifiers: 9936259308331
Academic Unit: King Abdulaziz University
Language: English
Resource Type: Journal article