{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T03:21:49Z","timestamp":1780370509811,"version":"3.54.1"},"reference-count":41,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","license":[{"start":{"date-parts":[[2021,4,1]],"date-time":"2021-04-01T00:00:00Z","timestamp":1617235200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circ: Genomic and Precision Medicine"],"published-print":{"date-parts":[[2021,4]]},"abstract":"<jats:sec>\n            <jats:title>Background:<\/jats:title>\n            <jats:p>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.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods:<\/jats:title>\n            <jats:p>There were 1522 participants of European ancestry from the COLCOT trial available for the pharmacogenomic study of COLCOT trial. The pharmacogenomic study\u2019s 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\u2019 DNA was genotyped using the Illumina Global Screening array followed by imputation. We performed a genome-wide association study in colchicine-treated patients.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results:<\/jats:title>\n            <jats:p>\n              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\u20132.35],\n              <jats:italic>P<\/jats:italic>\n              =7.41\u00d710\n              <jats:sup>\u22129<\/jats:sup>\n              ) in a locus which colocalizes with Crohn disease, and one with lead variant rs74795203 (hazard ratio, 2.51 [95% CI, 1.82\u20133.47];\n              <jats:italic>P<\/jats:italic>\n              =2.70\u00d710\n              <jats:sup>\u22128<\/jats:sup>\n              ), an intronic variant in gene\n              <jats:italic>SEPHS1<\/jats:italic>\n              . The interaction terms between the genetic variants and treatment with colchicine versus placebo were significant.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions:<\/jats:title>\n            <jats:p>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.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circgen.120.003183","type":"journal-article","created":{"date-parts":[[2021,2,9]],"date-time":"2021-02-09T17:15:05Z","timestamp":1612890905000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":16,"title":["Pharmacogenomics of the Efficacy and Safety of Colchicine in COLCOT"],"prefix":"10.1161","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8442-4393","authenticated-orcid":true,"given":"Marie-Pierre","family":"Dub\u00e9","sequence":"first","affiliation":[{"name":"Montreal Heart Institute (M.-P.D., M.-A.L., A.L., L.-P.L.P., R.F., G.A., S.P., A.B., M.S., M.C., L.B., I.M., A.D., D.R., N.B., M.S., S.d.D., P.L.L., M.-C.G., J.-C.T.), Universit\u00e9 de Montr\u00e9al, Canada."},{"name":"Universit\u00e9 de Montr\u00e9al Beaulieu-Saucier Pharmacogenomics Centre (M.-P.D., M.-A.L., A.L., L.-P.L.P., R.F., G.A., S.P., A.B., M.S., I.M., A.D., S.d.D.), Universit\u00e9 de Montr\u00e9al, Canada."},{"name":"Department of Medicine (M.-P.D., A.L., M.S., N.B., M.S., J.-C.T.), Universit\u00e9 de Montr\u00e9al, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6927-1210","authenticated-orcid":true,"given":"Marc-Andr\u00e9","family":"Legault","sequence":"additional","affiliation":[{"name":"Montreal Heart Institute (M.-P.D., M.-A.L., A.L., L.-P.L.P., R.F., G.A., S.P., A.B., M.S., M.C., L.B., I.M., A.D., D.R., N.B., M.S., S.d.D., P.L.L., M.-C.G., J.-C.T.), Universit\u00e9 de Montr\u00e9al, Canada."},{"name":"Universit\u00e9 de Montr\u00e9al Beaulieu-Saucier Pharmacogenomics Centre (M.-P.D., M.-A.L., A.L., L.-P.L.P., R.F., G.A., S.P., A.B., M.S., I.M., A.D., S.d.D.), Universit\u00e9 de Montr\u00e9al, Canada."},{"name":"Departments of Biochemistry and Molecular Medicine, Faculty of Medicine (M.-A.L.), Universit\u00e9 de Montr\u00e9al, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1817-7029","authenticated-orcid":true,"given":"Audrey","family":"Lema\u00e7on","sequence":"additional","affiliation":[{"name":"Montreal Heart Institute (M.-P.D., M.-A.L., A.L., L.-P.L.P., R.F., G.A., S.P., A.B., M.S., M.C., L.B., I.M., A.D., D.R., N.B., M.S., S.d.D., P.L.L., M.-C.G., J.-C.T.), Universit\u00e9 de Montr\u00e9al, Canada."},{"name":"Universit\u00e9 de Montr\u00e9al Beaulieu-Saucier Pharmacogenomics Centre (M.-P.D., M.-A.L., A.L., L.-P.L.P., R.F., G.A., S.P., A.B., M.S., I.M., A.D., S.d.D.), Universit\u00e9 de Montr\u00e9al, Canada."},{"name":"Department of Medicine (M.-P.D., A.L., M.S., N.B., M.S., J.-C.T.), Universit\u00e9 de Montr\u00e9al, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7423-0958","authenticated-orcid":true,"given":"Louis-Philippe","family":"Lemieux Perreault","sequence":"additional","affiliation":[{"name":"Montreal Heart Institute (M.-P.D., M.-A.L., A.L., L.-P.L.P., R.F., G.A., S.P., A.B., M.S., M.C., L.B., I.M., A.D., D.R., N.B., M.S., S.d.D., P.L.L., M.-C.G., J.-C.T.), Universit\u00e9 de Montr\u00e9al, Canada."},{"name":"Universit\u00e9 de Montr\u00e9al Beaulieu-Saucier Pharmacogenomics Centre (M.-P.D., M.-A.L., A.L., L.-P.L.P., R.F., G.A., S.P., A.B., M.S., I.M., A.D., S.d.D.), Universit\u00e9 de Montr\u00e9al, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ren\u00e9","family":"Fouodjio","sequence":"additional","affiliation":[{"name":"Montreal Heart Institute (M.-P.D., M.-A.L., A.L., L.-P.L.P., R.F., G.A., S.P., A.B., M.S., M.C., L.B., I.M., A.D., D.R., N.B., M.S., S.d.D., P.L.L., M.-C.G., J.-C.T.), Universit\u00e9 de Montr\u00e9al, Canada."},{"name":"Universit\u00e9 de Montr\u00e9al Beaulieu-Saucier Pharmacogenomics Centre (M.-P.D., M.-A.L., A.L., L.-P.L.P., R.F., G.A., S.P., A.B., M.S., I.M., A.D., S.d.D.), Universit\u00e9 de Montr\u00e9al, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2786-8198","authenticated-orcid":true,"given":"David D.","family":"Waters","sequence":"additional","affiliation":[{"name":"San Francisco General Hospital, CA (D.D.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0860-4135","authenticated-orcid":true,"given":"Simon","family":"Kouz","sequence":"additional","affiliation":[{"name":"Centre Hospitalier R\u00e9gional de Lanaudi\u00e8re, Joliette, Canada (S.K.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8034-4529","authenticated-orcid":true,"given":"Fausto J.","family":"Pinto","sequence":"additional","affiliation":[{"name":"Santa Maria University Hospital (CHULN), CAML, CCUL, Faculdade de Medicina da Universidade de Lisboa, Portugal (F.J.P.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2764-6779","authenticated-orcid":true,"given":"Aldo P.","family":"Maggioni","sequence":"additional","affiliation":[{"name":"Maria Cecilia Hospital, GVM Care and Research, Italy (A.P.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2181-9579","authenticated-orcid":true,"given":"Rafael","family":"Diaz","sequence":"additional","affiliation":[{"name":"Estudios Clinicos Latinoamerica, Rosario, Argentina (R.D.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4547-8636","authenticated-orcid":true,"given":"Colin","family":"Berry","sequence":"additional","affiliation":[{"name":"University of Glasgow, NHS Glasgow Clinical Research Facility, United Kingsom (C.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2064-9603","authenticated-orcid":true,"given":"Wolfgang","family":"Koenig","sequence":"additional","affiliation":[{"name":"Deutsches Herzzentrum M\u00fcnchen, Technische Universit\u00e4t M\u00fcnchen, Munich, Germany (W.K.)."},{"name":"DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany (W.K.)."},{"name":"Institute of Epidemiology and Medical Biometry, University of Ulm, Germany (W.K.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0871-9197","authenticated-orcid":true,"given":"Jose","family":"Lopez-Sendon","sequence":"additional","affiliation":[{"name":"H La Paz, IdiPaz, UAM, Ciber-CV Madrid, Spain (J.L.-S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Habib","family":"Gamra","sequence":"additional","affiliation":[{"name":"Fattouma Bourguiba University Hospital, Monastir, Tunisia (H.G.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0760-5929","authenticated-orcid":true,"given":"Ghassan S.","family":"Kiwan","sequence":"additional","affiliation":[{"name":"Bellevue Medical Centre, Beirut, Lebanon (G.S.K.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3702-2962","authenticated-orcid":true,"given":"G\u00e9raldine","family":"Asselin","sequence":"additional","affiliation":[{"name":"Montreal Heart Institute (M.-P.D., M.-A.L., A.L., L.-P.L.P., R.F., G.A., S.P., A.B., M.S., M.C., L.B., I.M., A.D., D.R., N.B., M.S., S.d.D., P.L.L., M.-C.G., J.-C.T.), Universit\u00e9 de Montr\u00e9al, Canada."},{"name":"Universit\u00e9 de Montr\u00e9al Beaulieu-Saucier Pharmacogenomics Centre (M.-P.D., M.-A.L., A.L., L.-P.L.P., R.F., G.A., S.P., A.B., M.S., I.M., A.D., S.d.D.), Universit\u00e9 de Montr\u00e9al, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvie","family":"Provost","sequence":"additional","affiliation":[{"name":"Montreal Heart Institute (M.-P.D., M.-A.L., A.L., L.-P.L.P., R.F., G.A., S.P., A.B., M.S., M.C., L.B., I.M., A.D., D.R., N.B., M.S., S.d.D., P.L.L., M.-C.G., J.-C.T.), Universit\u00e9 de Montr\u00e9al, Canada."},{"name":"Universit\u00e9 de Montr\u00e9al Beaulieu-Saucier Pharmacogenomics Centre (M.-P.D., M.-A.L., A.L., L.-P.L.P., R.F., G.A., S.P., A.B., M.S., I.M., A.D., S.d.D.), Universit\u00e9 de Montr\u00e9al, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amina","family":"Barhdadi","sequence":"additional","affiliation":[{"name":"Montreal Heart Institute (M.-P.D., M.-A.L., A.L., L.-P.L.P., R.F., G.A., S.P., A.B., M.S., M.C., L.B., I.M., A.D., D.R., N.B., M.S., S.d.D., P.L.L., M.-C.G., J.-C.T.), Universit\u00e9 de Montr\u00e9al, Canada."},{"name":"Universit\u00e9 de Montr\u00e9al Beaulieu-Saucier Pharmacogenomics Centre (M.-P.D., M.-A.L., A.L., L.-P.L.P., R.F., G.A., S.P., A.B., M.S., I.M., A.D., S.d.D.), Universit\u00e9 de Montr\u00e9al, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0539-3646","authenticated-orcid":true,"given":"Maxine","family":"Sun","sequence":"additional","affiliation":[{"name":"Montreal Heart Institute (M.-P.D., M.-A.L., A.L., L.-P.L.P., R.F., G.A., S.P., A.B., M.S., M.C., L.B., I.M., A.D., D.R., N.B., M.S., S.d.D., P.L.L., M.-C.G., J.-C.T.), Universit\u00e9 de Montr\u00e9al, Canada."},{"name":"Universit\u00e9 de Montr\u00e9al Beaulieu-Saucier Pharmacogenomics Centre (M.-P.D., M.-A.L., A.L., L.-P.L.P., R.F., G.A., S.P., A.B., M.S., I.M., A.D., S.d.D.), Universit\u00e9 de Montr\u00e9al, Canada."},{"name":"Department of Medicine (M.-P.D., A.L., M.S., N.B., M.S., J.-C.T.), Universit\u00e9 de Montr\u00e9al, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mari\u00e8ve","family":"Cossette","sequence":"additional","affiliation":[{"name":"Montreal Heart Institute (M.-P.D., M.-A.L., A.L., L.-P.L.P., R.F., G.A., S.P., A.B., M.S., M.C., L.B., I.M., A.D., D.R., N.B., M.S., S.d.D., P.L.L., M.-C.G., J.-C.T.), Universit\u00e9 de Montr\u00e9al, Canada."},{"name":"Montreal Health Innovation Coordinating Centre, Canada (M.C., L.B., M.-C.G.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucie","family":"Blondeau","sequence":"additional","affiliation":[{"name":"Montreal Heart Institute (M.-P.D., M.-A.L., A.L., L.-P.L.P., R.F., G.A., S.P., A.B., M.S., M.C., L.B., I.M., A.D., D.R., N.B., M.S., S.d.D., P.L.L., M.-C.G., J.-C.T.), Universit\u00e9 de Montr\u00e9al, Canada."},{"name":"Montreal Health Innovation Coordinating Centre, Canada (M.C., L.B., M.-C.G.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1580-8961","authenticated-orcid":true,"given":"Ian","family":"Mongrain","sequence":"additional","affiliation":[{"name":"Montreal Heart Institute (M.-P.D., M.-A.L., A.L., L.-P.L.P., R.F., G.A., S.P., A.B., M.S., M.C., L.B., I.M., A.D., D.R., N.B., M.S., S.d.D., P.L.L., M.-C.G., J.-C.T.), Universit\u00e9 de Montr\u00e9al, Canada."},{"name":"Universit\u00e9 de Montr\u00e9al Beaulieu-Saucier Pharmacogenomics Centre (M.-P.D., M.-A.L., A.L., L.-P.L.P., R.F., G.A., S.P., A.B., M.S., I.M., A.D., S.d.D.), Universit\u00e9 de Montr\u00e9al, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2969-9877","authenticated-orcid":true,"given":"Anick","family":"Dubois","sequence":"additional","affiliation":[{"name":"Montreal Heart Institute (M.-P.D., M.-A.L., A.L., L.-P.L.P., R.F., G.A., S.P., A.B., M.S., M.C., L.B., I.M., A.D., D.R., N.B., M.S., S.d.D., P.L.L., M.-C.G., J.-C.T.), Universit\u00e9 de Montr\u00e9al, Canada."},{"name":"Universit\u00e9 de Montr\u00e9al Beaulieu-Saucier Pharmacogenomics Centre (M.-P.D., M.-A.L., A.L., L.-P.L.P., R.F., G.A., S.P., A.B., M.S., I.M., A.D., S.d.D.), Universit\u00e9 de Montr\u00e9al, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1572-4146","authenticated-orcid":true,"given":"David","family":"Rhainds","sequence":"additional","affiliation":[{"name":"Montreal Heart Institute (M.-P.D., M.-A.L., A.L., L.-P.L.P., R.F., G.A., S.P., A.B., M.S., M.C., L.B., I.M., A.D., D.R., N.B., M.S., S.d.D., P.L.L., M.-C.G., J.-C.T.), Universit\u00e9 de Montr\u00e9al, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9201-5810","authenticated-orcid":true,"given":"Nadia","family":"Bouabdallaoui","sequence":"additional","affiliation":[{"name":"Montreal Heart Institute (M.-P.D., M.-A.L., A.L., L.-P.L.P., R.F., G.A., S.P., A.B., M.S., M.C., L.B., I.M., A.D., D.R., N.B., M.S., S.d.D., P.L.L., M.-C.G., J.-C.T.), Universit\u00e9 de Montr\u00e9al, Canada."},{"name":"Department of Medicine (M.-P.D., A.L., M.S., N.B., M.S., J.-C.T.), Universit\u00e9 de Montr\u00e9al, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9674-6565","authenticated-orcid":true,"given":"Michelle","family":"Samuel","sequence":"additional","affiliation":[{"name":"Montreal Heart Institute (M.-P.D., M.-A.L., A.L., L.-P.L.P., R.F., G.A., S.P., A.B., M.S., M.C., L.B., I.M., A.D., D.R., N.B., M.S., S.d.D., P.L.L., M.-C.G., J.-C.T.), Universit\u00e9 de Montr\u00e9al, Canada."},{"name":"Department of Medicine (M.-P.D., A.L., M.S., N.B., M.S., J.-C.T.), Universit\u00e9 de Montr\u00e9al, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5404-7929","authenticated-orcid":true,"given":"Simon","family":"de Denus","sequence":"additional","affiliation":[{"name":"Montreal Heart Institute (M.-P.D., M.-A.L., A.L., L.-P.L.P., R.F., G.A., S.P., A.B., M.S., M.C., L.B., I.M., A.D., D.R., N.B., M.S., S.d.D., P.L.L., M.-C.G., J.-C.T.), Universit\u00e9 de Montr\u00e9al, Canada."},{"name":"Universit\u00e9 de Montr\u00e9al Beaulieu-Saucier Pharmacogenomics Centre (M.-P.D., M.-A.L., A.L., L.-P.L.P., R.F., G.A., S.P., A.B., M.S., I.M., A.D., S.d.D.), Universit\u00e9 de Montr\u00e9al, Canada."},{"name":"Universit\u00e9 de Montr\u00e9al, Faculty of Pharmacy, Canada (S.d.D.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe L.","family":"L\u2019Allier","sequence":"additional","affiliation":[{"name":"Montreal Heart Institute (M.-P.D., M.-A.L., A.L., L.-P.L.P., R.F., G.A., S.P., A.B., M.S., M.C., L.B., I.M., A.D., D.R., N.B., M.S., S.d.D., P.L.L., M.-C.G., J.-C.T.), Universit\u00e9 de Montr\u00e9al, 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