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Pharmacogenomics of the efficacy and safety of Colchicine in COLCOT

2021Journal article Open access
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dc.contributor.authorDubé, Marie-Pierre
dc.contributor.authorLegault, Marc-André
dc.contributor.authorLemaçon, Audrey
dc.contributor.authorLemieux Perreault, Louis-Philippe
dc.contributor.authorFouodjio, René
dc.contributor.authorWaters, David D.
dc.contributor.authorKouz, Simon
dc.contributor.authorPinto, Fausto J.
dc.contributor.authorMaggioni, Aldo P.
dc.contributor.authorDiaz, Rafael
dc.contributor.authorBerry, Colin
dc.contributor.authorKoenig, Wolfgang
dc.contributor.authorLopez-Sendon, Jose
dc.contributor.authorGamra, Habib
dc.contributor.authorKiwan, Ghassan S.
dc.contributor.authorAsselin, Géraldine
dc.contributor.authorProvost, Sylvie
dc.contributor.authorBarhdadi, Amina
dc.contributor.authorSun, Maxine
dc.contributor.authorCossette, Mariève
dc.contributor.authorBlondeau, Lucie
dc.contributor.authorMongrain, Ian
dc.contributor.authorDubois, Anick
dc.contributor.authorRhainds, David
dc.contributor.authorBouabdallaoui, Nadia
dc.contributor.authorSamuel, Michelle
dc.contributor.authorde Denus, Simon
dc.contributor.authorL’Allier, Philippe L.
dc.contributor.authorGuertin, Marie-Claude
dc.contributor.authorRoubille, François
dc.contributor.authorTardif, Jean-Claude
dc.date.accessioned2021-07-28T14:27:21Z
dc.date.available2021-07-28T14:27:21Z
dc.date.issued2021
dc.description© 2021 The Authors. Circulation: Genomic and Precision Medicine is published on behalf of the American Heart Association, Inc., by Wolters Kluwer Health, Inc. This is an open access article under the terms of the Creative Commons Attribution Non-Commercial License, which permits use, distribution, and reproduction in any medium, provided that the original work is properly cited and is not used for commercial purposes.pt_PT
dc.description.abstractBackground: 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=7.41×10-9) 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=2.70×10-8), 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.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationCirc Genom Precis Med. 2021 Apr;14(2):e003183pt_PT
dc.identifier.doi10.1161/CIRCGEN.120.003183pt_PT
dc.identifier.eissn2574-8300
dc.identifier.urihttp://hdl.handle.net/10451/49191
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherAmerican Heart Associationpt_PT
dc.relation.publisherversionhttps://www.ahajournals.org/journal/circgenpt_PT
dc.rights.urihttp://creativecommons.org/licenses/by-nc/4.0/pt_PT
dc.subjectAcute coronary syndromept_PT
dc.subjectColchicinept_PT
dc.subjectGastrointestinal diseasespt_PT
dc.subjectMyocardial infarctionpt_PT
dc.subjectPharmacogeneticspt_PT
dc.titlePharmacogenomics of the efficacy and safety of Colchicine in COLCOTpt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.issue2pt_PT
oaire.citation.titleCirculation: Genomic and Precision Medicinept_PT
oaire.citation.volume14pt_PT
person.familyNamePinto
person.givenNameFausto J.
person.identifier1308889
person.identifier.ciencia-idC311-AEDD-6DBB
person.identifier.orcid0000-0002-8034-4529
person.identifier.ridG-9363-2015
person.identifier.scopus-author-id7102740158
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
relation.isAuthorOfPublication5f44176f-69f5-482c-83cd-ab94425a6ec3
relation.isAuthorOfPublication.latestForDiscovery5f44176f-69f5-482c-83cd-ab94425a6ec3

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