Pharmacogenomics of the efficacy and safety of Colchicine in COLCOT
| Autor(a) principal: | |
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| Data de Publicação: | 2021 |
| Outros Autores: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
| Texto Completo: | http://hdl.handle.net/10451/49191 |
Resumo: | © 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. |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Pharmacogenomics of the efficacy and safety of Colchicine in COLCOTAcute coronary syndromeColchicineGastrointestinal diseasesMyocardial infarctionPharmacogenetics© 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.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=7.41×10-9) 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.American Heart AssociationRepositório da Universidade de LisboaDubé, Marie-PierreLegault, Marc-AndréLemaçon, AudreyLemieux Perreault, Louis-PhilippeFouodjio, RenéWaters, David D.Kouz, SimonPinto, Fausto J.Maggioni, Aldo P.Diaz, RafaelBerry, ColinKoenig, WolfgangLopez-Sendon, JoseGamra, HabibKiwan, Ghassan S.Asselin, GéraldineProvost, SylvieBarhdadi, AminaSun, MaxineCossette, MarièveBlondeau, LucieMongrain, IanDubois, AnickRhainds, DavidBouabdallaoui, NadiaSamuel, Michellede Denus, SimonL’Allier, Philippe L.Guertin, Marie-ClaudeRoubille, FrançoisTardif, Jean-Claude2021-07-28T14:27:21Z20212021-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10451/49191engCirc Genom Precis Med. 2021 Apr;14(2):e00318310.1161/CIRCGEN.120.0031832574-8300info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-11-08T16:52:40Zoai:repositorio.ul.pt:10451/49191Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T22:00:49.001623Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
| dc.title.none.fl_str_mv |
Pharmacogenomics of the efficacy and safety of Colchicine in COLCOT |
| title |
Pharmacogenomics of the efficacy and safety of Colchicine in COLCOT |
| spellingShingle |
Pharmacogenomics of the efficacy and safety of Colchicine in COLCOT Dubé, Marie-Pierre Acute coronary syndrome Colchicine Gastrointestinal diseases Myocardial infarction Pharmacogenetics |
| title_short |
Pharmacogenomics of the efficacy and safety of Colchicine in COLCOT |
| title_full |
Pharmacogenomics of the efficacy and safety of Colchicine in COLCOT |
| title_fullStr |
Pharmacogenomics of the efficacy and safety of Colchicine in COLCOT |
| title_full_unstemmed |
Pharmacogenomics of the efficacy and safety of Colchicine in COLCOT |
| title_sort |
Pharmacogenomics of the efficacy and safety of Colchicine in COLCOT |
| author |
Dubé, Marie-Pierre |
| author_facet |
Dubé, Marie-Pierre Legault, Marc-André Lemaçon, Audrey Lemieux Perreault, Louis-Philippe Fouodjio, René Waters, David D. Kouz, Simon Pinto, Fausto J. Maggioni, Aldo P. Diaz, Rafael Berry, Colin Koenig, Wolfgang Lopez-Sendon, Jose Gamra, Habib Kiwan, Ghassan S. Asselin, Géraldine Provost, Sylvie Barhdadi, Amina Sun, Maxine Cossette, Mariève Blondeau, Lucie Mongrain, Ian Dubois, Anick Rhainds, David Bouabdallaoui, Nadia Samuel, Michelle de Denus, Simon L’Allier, Philippe L. Guertin, Marie-Claude Roubille, François Tardif, Jean-Claude |
| author_role |
author |
| author2 |
Legault, Marc-André Lemaçon, Audrey Lemieux Perreault, Louis-Philippe Fouodjio, René Waters, David D. Kouz, Simon Pinto, Fausto J. Maggioni, Aldo P. Diaz, Rafael Berry, Colin Koenig, Wolfgang Lopez-Sendon, Jose Gamra, Habib Kiwan, Ghassan S. Asselin, Géraldine Provost, Sylvie Barhdadi, Amina Sun, Maxine Cossette, Mariève Blondeau, Lucie Mongrain, Ian Dubois, Anick Rhainds, David Bouabdallaoui, Nadia Samuel, Michelle de Denus, Simon L’Allier, Philippe L. Guertin, Marie-Claude Roubille, François Tardif, Jean-Claude |
| author2_role |
author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
Repositório da Universidade de Lisboa |
| dc.contributor.author.fl_str_mv |
Dubé, Marie-Pierre Legault, Marc-André Lemaçon, Audrey Lemieux Perreault, Louis-Philippe Fouodjio, René Waters, David D. Kouz, Simon Pinto, Fausto J. Maggioni, Aldo P. Diaz, Rafael Berry, Colin Koenig, Wolfgang Lopez-Sendon, Jose Gamra, Habib Kiwan, Ghassan S. Asselin, Géraldine Provost, Sylvie Barhdadi, Amina Sun, Maxine Cossette, Mariève Blondeau, Lucie Mongrain, Ian Dubois, Anick Rhainds, David Bouabdallaoui, Nadia Samuel, Michelle de Denus, Simon L’Allier, Philippe L. Guertin, Marie-Claude Roubille, François Tardif, Jean-Claude |
| dc.subject.por.fl_str_mv |
Acute coronary syndrome Colchicine Gastrointestinal diseases Myocardial infarction Pharmacogenetics |
| topic |
Acute coronary syndrome Colchicine Gastrointestinal diseases Myocardial infarction Pharmacogenetics |
| 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. |
| publishDate |
2021 |
| dc.date.none.fl_str_mv |
2021-07-28T14:27:21Z 2021 2021-01-01T00:00:00Z |
| dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
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article |
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publishedVersion |
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http://hdl.handle.net/10451/49191 |
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http://hdl.handle.net/10451/49191 |
| dc.language.iso.fl_str_mv |
eng |
| language |
eng |
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Circ Genom Precis Med. 2021 Apr;14(2):e003183 10.1161/CIRCGEN.120.003183 2574-8300 |
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info:eu-repo/semantics/openAccess |
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openAccess |
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application/pdf |
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American Heart Association |
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American Heart Association |
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reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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