Evidence map›Paper›PMID 30506689›Full record

SynthesisClinical pharmacology and therapeutics2019

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 and 73 more

Erratum issuedOpen access · bronzeAbstract readMeta-Analysis
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in Clinical pharmacology and therapeutics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 17 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed, 3 pooled it
3.0field-weighted citation impact, top 10% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

17 citing papers in PubMed, 3 syntheses or guidelines pooled it, 32 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Guideline
  4. The impact ofFrontiers in pharmacology · 2025
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  6. Review
  7. Cardiovascular precision medicine - A pharmacogenomic perspective.Cambridge prisms. Precision medicine · 2023
    Review
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  9. Article
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

83 authors at 20 institutions in 21 countries.

Elisa DaneseClinical Biochemistry Section, Department of Neurological, Biomedical and Movement Sciences, University of Verona, Verona, Italy.
Sara RaimondiGeneral Medicine and Hypertension Unit, Department of Medicine, University of Verona, Verona, Italy.
Martina MontagnanaClinical Biochemistry Section, Department of Neurological, Biomedical and Movement Sciences, University of Verona, Verona, Italy.
Angela TagettiGeneral Medicine and Hypertension Unit, Department of Medicine, University of Verona, Verona, Italy.
Taimour LangaeeDepartment of Pharmacotherapy and Translational Research, Center for Pharmacogenomics, College of Pharmacy, University of Florida, Gainesville, Florida, USA.
Paola BorgianiGenetics Section, Department of Biomedicine and Prevention, University of Rome "Tor Vergata,", Rome, Italy.
Cinzia CiccacciGenetics Section, Department of Biomedicine and Prevention, University of Rome "Tor Vergata,", Rome, Italy.
Antonio J CarcasClinical Pharmacology Department, La Paz University Hospital, School of Medicine, IdiPAZ, Universidad Autónoma de Madrid, Madrid, Spain.
Alberto M BorobiaClinical Pharmacology Department, La Paz University Hospital, School of Medicine, IdiPAZ, Universidad Autónoma de Madrid, Madrid, Spain.
Hoi Y TongClinical Pharmacology Department, La Paz University Hospital, School of Medicine, IdiPAZ, Universidad Autónoma de Madrid, Madrid, Spain.
Cristina Dávila-FajardoDepartment of Clinical Pharmacy, San Cecilio University Hospital, Institute for Biomedical Research, IBS, Granada, Spain.
Mariana Rodrigues BottonDepartamento de Genética, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
Stephane BourgeoisWilliam Harvey Research Institute, Barts & the London Medical School, Queen Mary University of London, London, UK.
Panos DeloukasWilliam Harvey Research Institute, Barts & the London Medical School, Queen Mary University of London, London, UK.ORCID 0000-0001-9251-070X
Michael D CaldwellCenter for Hyperbaric Medicine and Tissue Repair, Marshfield Clinic, Marshfield, Wisconsin, USA.
Jim K BurmesterGrants Office, Gundersen Health System, La Crosse, Wisconsin, USA.
Richard L BergClinical Research Center, Marshfield Clinic Research Foundation, Marshfield, Wisconsin, USA.
Larisa H CavallariDepartment of Pharmacotherapy and Translational Research, Center for Pharmacogenomics, College of Pharmacy, University of Florida, Gainesville, Florida, USA.
Katarzyna DrozdaDepartment of Pharmacy Practice, University of Illinois at Chicago, Chicago, Illinois, USA.
Min HuangSchool of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, China.
Li-Zi ZhaoSchool of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, China.
Han-Jing CenGuangzhou Women and Children's Medical Center, Guangzhou, China.
Rocio Gonzalez-ConejeroCentro Regional de Hemodonación, Hospital Universitario Morales Meseguer, Universidad de Murcia, Murcia, Spain.
Vanessa RoldanCentro Regional de Hemodonación, Hospital Universitario Morales Meseguer, Universidad de Murcia, Murcia, Spain.ORCID 0000-0002-4945-6602
Yusuke NakamuraResearch Group for Pharmacogenomics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
Taisei MushirodaResearch Group for Pharmacogenomics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
Inna Y GongDivision of Clinical Pharmacology, Department of Medicine, University of Western Ontario, London, Ontario, Canada.
Richard B KimDivision of Clinical Pharmacology, Department of Medicine, University of Western Ontario, London, Ontario, Canada.
Keita HiraiDepartment of Clinical Pharmacology & Genetics, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan.ORCID 0000-0001-8027-3508
Kunihiko ItohDepartment of Clinical Pharmacology & Genetics, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan.
Carlos IsazaFaculty of Heath Sciences, Laboratory of Medical Genetics, Universidad Tecnológica de Pereira, Pereira, Colombia.
Leonardo BeltránFaculty of Heath Sciences, Laboratory of Medical Genetics, Universidad Tecnológica de Pereira, Pereira, Colombia.ORCID 0000-0001-6287-6815
Enrique Jiménez-VaroClinical Laboratory Department, Hospital La Línea, Cádiz, Spain.
Marisa Cañadas-GarreCentre for Public Health, School of Medicine, Dentistry, and Biomedical Sciences, Queen's University Belfast, Belfast, UK.ORCID 0000-0003-1103-5658
Alice GiontellaGeneral Medicine and Hypertension Unit, Department of Medicine, University of Verona, Verona, Italy.
Marianne K KringenDepartment of Pharmacology, Oslo University Hospital, Ullevål, Oslo, Norway.
Kari Bente Foss HaugDepartment of Medical Biochemistry, Oslo University Hospital, Ullevål, Oslo, Norway.
Hye Sun GwakDivision of Life and Pharmaceutical Sciences, College of Pharmacy, Ewha Womans University, Seoul, Korea.ORCID 0000-0003-0278-2563
Kyung Eun LeeCollege of Pharmacy, Chungbuk National University, Cheongju-si, Korea.ORCID 0000-0002-9535-7314
Pietro MinuzGeneral Medicine and Hypertension Unit, Department of Medicine, University of Verona, Verona, Italy.ORCID 0000-0001-5450-2186
Ming Ta Michael LeeGenomic Medicine Institute, Geisinger Health System, Danville, Pennsylvania, USA.ORCID 0000-0003-1769-6895
Steven A LubitzCardiac Arrhythmia Service & Cardiovascular Research Center, Massachusetts General Hospital, Boston, Massachusetts, USA.
Stuart ScottDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA.ORCID 0000-0001-5720-1864
Cristina MazzaccaraCEINGE-Biotecnologie Avanzate s.c.ar.l., Napoli, Italy.
Lucia SacchettiCEINGE-Biotecnologie Avanzate s.c.ar.l., Napoli, Italy.
Ece GençDepartment of Pharmacology, Yeditepe University, Istanbul, Turkey.
Mahmut ÖzerDepartment of Pharmacology, Yeditepe University, Istanbul, Turkey.
Anil PathareCollege of Medicine & Health Sciences, Sultan Qaboos University, Muscat, Oman.
Rajagopal KrishnamoorthyINSERM, UMR_S 763, Paris, France.
Andras PaldiEcole Pratique des Hautes Etudes, UMRS_951, Genethon, Evry, France.
Virginie SiguretSorbonne Paris Cité, INSERM, UMR-S-1140, Université Paris Descartes, Paris, France.
Marie-Anne LoriotSorbonne Paris Cité, INSERM, UMR-S-1147, Université Paris Descartes, Paris, France.
Vijay Kumar KutalaDepartment of Clinical Pharmacology & Therapeutics, Nizam's Institute of Medical Sciences, Hyderabad, India.
Guilherme Suarez-KurtzCoordenação de Pesquisa, Instituto Nacional de Câncer, Rio de Janeiro, Brazil.
Jamila PeriniResearch Laboratory of Pharmaceutical Sciences, West Zone State University-UEZO, Rio de Janeiro, Brazil.
Josh C DennyDepartment of Medicine and Department of Biomedical Informatics, Vanderbilt University, Nashville, Tennessee, USA.ORCID 0000-0002-3049-7332
Andrea H RamirezDepartment of Medicine, Vanderbilt University, Nashville, Tennessee, USA.
Balraj MittalDepartment of Biotechnology, Babasaheb Bhimrao Ambedkar University, Lucknow, India.
Saurabh Singh RathoreDepartment of Biotechnology, Babasaheb Bhimrao Ambedkar University, Lucknow, India.
Hersh SagreiyaDepartment of Genetics, Stanford University School of Medicine, Stanford, California, USA.
Russ AltmanDepartment of Genetics, Stanford University School of Medicine, Stanford, California, USA.ORCID 0000-0003-3859-2905
Mohamed Hossam A ShahinDepartment of Pharmacotherapy and Translational Research, Center for Pharmacogenomics, College of Pharmacy, University of Florida, Gainesville, Florida, USA.
Sherief I KhalifaCollege of Pharmacy, Gulf Medical University, Ajman, United Arab Emirates.
Nita A LimdiDepartment of Neurology, University of Alabama at Birmingham, Birmingham, Alabama, USA.
Charles RiversDepartment of Neurology, University of Alabama at Birmingham, Birmingham, Alabama, USA.
Aditi ShendreDepartment of Epidemiology, Richard M. Fairbanks School of Public Health, Indiana University Purdue University, Indianapolis, Indiana, USA.ORCID 0000-0003-4123-7613
Chrisly DillonDepartment of Neurology, University of Alabama at Birmingham, Birmingham, Alabama, USA.
Ivet M SuriapranataMochtar Riady Institute for Nanotechnology, Universitas Pelita Harapan, Lippo Karawaci, Tangerang, Banten, Indonesia.
Hong-Hao ZhouInstitute of Clinical Pharmacology, Central South University, Hunan Sheng, China.
Sheng-Lan TanDepartment of Pharmacy, Xiangya Second Hospital, Central South University, Hunan Sheng, China.
Vacis TatarunasLaboratory of Molecular Cardiology, Institute of Cardiology, Lithuanian University of Health Sciences, Kaunas, Lithuania.
Vaiva LesauskaiteLaboratory of Molecular Cardiology, Institute of Cardiology, Lithuanian University of Health Sciences, Kaunas, Lithuania.
Yumao ZhangDivision of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.ORCID 0000-0001-8027-5431
Anke H Maitland-van der ZeeDivision of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.
Talitha I VerhoefDepartment of Applied Health Research, University College London, London, UK.
Anthonius de BoerDivision of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.
Monica TaljaardClinica Epidemiology Program and Department of Epidemiology and Community Medicine, Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Ontario, Canada.
Carlo Federico ZambonDepartment of Medicine-DIMED, University of Padua, Padua, Italy.ORCID 0000-0002-4244-879X
Vittorio PengoDepartment of Cardiac, Thoracic and Vascular Sciences, University of Padua, Padua, Italy.
Jieying Eunice ZhangWolfson Centre for Personalised Medicine, Department of Molecular and Clinical Pharmacology, University of Liverpool, Liverpool, UK.
Munir PirmohamedWolfson Centre for Personalised Medicine, Department of Molecular and Clinical Pharmacology, University of Liverpool, Liverpool, UK.ORCID 0000-0002-7534-7266
Julie A JohnsonDepartment of Pharmacotherapy and Translational Research, Center for Pharmacogenomics, College of Pharmacy, University of Florida, Gainesville, Florida, USA.
Cristiano FavaGeneral Medicine and Hypertension Unit, Department of Medicine, University of Verona, Verona, Italy.ORCID 0000-0002-1041-0842
University of Verona · ITAmerican Association of Colleges of Pharmacy · USHospital Universitario La Paz · ESUniversity of Alabama at Birmingham · USUtrecht University · NLBabasaheb Bhimrao Ambedkar University · INCeinge Biotecnologie Avanzate (Italy) · ITCentral South University · CNCentro Regional de Hemodonación · ESDélégation Paris 5 · FRLithuanian University of Health Sciences · LTMarshfield Clinic · USOslo University Hospital · NOQueen Mary University of London · GBRIKEN Center for Integrative Medical Sciences · JPStanford University · USSun Yat-sen University · CNTechnological University of Pereira · COUniversity of Liverpool · GBUniversity of Padua · IT

Funding

Pharmacogenomic Evaluation of Antihypertensive ResponsesU01GM074492 · NIGMS · UNIVERSITY OF FLORIDA · PI JOHNSON, JULIE A. · 2005 to 2014
$20.7M
STANFORD CANCER IMAGING TRAINING (SCIT) PROGRAMT32CA009695 · NCI · STANFORD UNIVERSITY · PI BRUCE L DANIEL, Jeremy Dahl · 1993 to 2026
$7.7M
Hypertension PharmacogeneticsR01HL074730 · NHLBI · UNIVERSITY OF FLORIDA · PI JOHNSON, JULIE A. · 2003 to 2006
$3.4M
Genomics of Cardiac ArrhythmiasR01HL139731 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI ELLINOR, PATRICK THOMAS · 2018 to 2022
$3.3M
British Heart Foundation RG/14/5/30893Department of HealthMedical Research Council MR/L006758/1NCI NIH HHS T32 CA009695NHLBI NIH HHS R01 HL074730NHLBI NIH HHS R01 HL139731NIGMS NIH HHS U01 GM074492
6 · The paper itself

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.

Indexed as

AgedAged, 80 and overCohort StudiesCoumarinsCytochrome P-450 CYP2C9Cytochrome P450 Family 4Dose-Response Relationship, DrugFemaleHumansMaleMiddle AgedPolymorphism, Single NucleotideVitamin K Epoxide ReductasescoumarinCoumarinsCYP2C9 protein, humanCYP4F2 protein, humanCytochrome P-450 CYP2C9Cytochrome P450 Family 4Vitamin K Epoxide ReductasesVKORC1 protein, human

Identifiers

PMID30506689
PMCPMC6542461
OpenAlexW2902167120

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.