Journal article
Pharmacogenomics of the Efficacy and Safety of Colchicine in COLCOT
Circulation. Genomic and precision medicine, v 14(2), pp 223-229
01 Apr 2021
PMID: 33560138
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Background:
The randomized, placebo-controlled COLCOT (Colchicine Cardiovascular Outcomes Trial) has shown the benefits of colchicine 0.5 mg daily to lower the rate of ischemic cardiovascular events in patients with a recent myocardial infarction. Here, we conducted a post hoc pharmacogenomic study of COLCOT with the aim to identify genetic predictors of the efficacy and safety of treatment with colchicine.
Methods:
There were 1522 participants of European ancestry from the COLCOT trial available for the pharmacogenomic study of COLCOT trial. The pharmacogenomic study's primary cardiovascular end point was defined as for the main trial, as time to first occurrence of cardiovascular death, resuscitated cardiac arrest, myocardial infarction, stroke, or urgent hospitalization for angina requiring coronary revascularization. The safety end point was time to the first report of gastrointestinal events. Patients' DNA was genotyped using the Illumina Global Screening array followed by imputation. We performed a genome-wide association study in colchicine-treated patients.
Results:
None of the genetic variants passed the genome-wide association study significance threshold for the primary cardiovascular end point conducted in 702 patients in the colchicine arm who were compliant to medication. The genome-wide association study for gastrointestinal events was conducted in all 767 patients in the colchicine arm and found 2 significant association signals, one with lead variant rs6916345 (hazard ratio, 1.89 [95% CI, 1.52-2.35], P=7.41x10(-9)) in a locus which colocalizes with Crohn disease, and one with lead variant rs74795203 (hazard ratio, 2.51 [95% CI, 1.82-3.47]; P=2.70x10(-8)), an intronic variant in gene SEPHS1. The interaction terms between the genetic variants and treatment with colchicine versus placebo were significant.
Conclusions:
We found 2 genomic regions associated with gastrointestinal events in patients treated with colchicine. Those findings will benefit from replication to confirm that some patients may have genetic predispositions to lower tolerability of treatment with colchicine.
Metrics
2 Record Views
Details
- Title
- Pharmacogenomics of the Efficacy and Safety of Colchicine in COLCOT
- Creators
- Marie-Pierre Dube - Montreal Heart InstituteMarc-Andre Legault - Montreal Heart InstituteAudrey Lemacon - Montreal Heart InstituteLouis-Philippe Lemieux Perreault - Montreal Heart InstituteRene Fouodjio - Montreal Heart InstituteDavid D. Waters - San Francisco General HospitalSimon Kouz - Cegep regional de LanaudiereFausto J. Pinto - Hospital de Santa MariaAldo P. Maggioni - Maria Cecilia HospitalRafael Diaz - Estudios Clínicos LatinoaméricaColin Berry - University of GlasgowWolfgang Koenig - German Centre for Cardiovascular ResearchJose Lopez-Sendon - Universidad Autónoma de MadridHabib Gamra - Hospital Fatuma Bourguiba MonastirGhassan S. Kiwan - Bellevue Hospital CenterGeraldine Asselin - Montreal Heart InstituteSylvie Provost - Montreal Heart InstituteAmina Barhdadi - Montreal Heart InstituteMaxine Sun - Montreal Heart InstituteMarieve Cossette - Montreal Heart InstituteLucie Blondeau - Montreal Heart InstituteIan Mongrain - Montreal Heart InstituteAnick Dubois - Montreal Heart InstituteDavid Rhainds - Montreal Heart InstituteNadia Bouabdallaoui - Montreal Heart InstituteMichelle Samuel - Montreal Heart InstituteSimon de Denus - Montreal Heart InstitutePhilippe L. L'Allier - Montreal Heart InstituteMarie-Claude Guertin - Montreal Heart InstituteFrancois Roubille - Centre National de la Recherche ScientifiqueJean-Claude Tardif - Montreal Heart Institute
- Publication Details
- Circulation. Genomic and precision medicine, v 14(2), pp 223-229
- Publisher
- Lippincott Williams & Wilkins
- Number of pages
- 7
- Grant note
- RE/18/6134217 / British Heart Foundation Frederick Banting and Charles Best Canada Graduate Scholarship Doctoral Award from the Canadian Institutes of Health Research (CIHR); Canadian Institutes of Health Research (CIHR) Health Collaboration Acceleration Fund from the Government of Quebec
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- General Internal Medicine
- Web of Science ID
- WOS:000641550000007
- Scopus ID
- 2-s2.0-85104654765
- Other Identifier
- 991022135634604721
UN Sustainable Development Goals (SDGs)
This publication has contributed to the advancement of the following goals:
InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Cardiac & Cardiovascular Systems
- Genetics & Heredity