{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T02:03:23Z","timestamp":1791597803419,"version":"4.3.4"},"reference-count":32,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","content-domain":{"domain":["ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circ Cardiovasc Genet"],"published-print":{"date-parts":[[2016,8]]},"abstract":"<jats:sec>\n            <jats:title>Background\u2014<\/jats:title>\n            <jats:p>Dalcetrapib effects on cardiovascular outcomes are determined by adenylate cyclase 9 gene polymorphisms. Our aim was to determine whether these clinical end point results are also associated with changes in reverse cholesterol transport and inflammation.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods and Results\u2014<\/jats:title>\n            <jats:p>\n              Participants of the dal-OUTCOMES and dal-PLAQUE-2 trials were randomly assigned to receive dalcetrapib or placebo in addition to standard care. High-sensitivity C-reactive protein was measured at baseline and at end of study in 5243 patients from dal-OUTCOMES also genotyped for the rs1967309 polymorphism in adenylate cyclase 9. Cholesterol efflux capacity of high-density lipoproteins from J774 macrophages after cAMP stimulation was determined at baseline and 12 months in 171 genotyped patients from dal-PLAQUE-2. Treatment with dalcetrapib resulted in placebo-adjusted geometric mean percent increases in high-sensitivity C-reactive protein from baseline to end of trial of 18.1% (\n              <jats:italic>P<\/jats:italic>\n              =0.0009) and 18.7% (\n              <jats:italic>P<\/jats:italic>\n              =0.00001) in participants with the GG and AG genotypes, respectively, but the change was \u22121.0% (\n              <jats:italic>P<\/jats:italic>\n              =0.89) in those with the protective AA genotype. There was an interaction between the treatment arm and the genotype groups (\n              <jats:italic>P<\/jats:italic>\n              =0.02). Although the mean change in cholesterol efflux was similar among study arms in patients with GG genotype (mean: 7.8% and 7.4%), increases were 22.3% and 3.5% with dalcetrapib and placebo for those with AA genotype (\n              <jats:italic>P<\/jats:italic>\n              =0.005). There was a significant genetic effect for change in efflux for dalcetrapib (\n              <jats:italic>P<\/jats:italic>\n              =0.02), but not with placebo.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions\u2014<\/jats:title>\n            <jats:p>Genotype-dependent effects on C-reactive protein and cholesterol efflux are supportive of dalcetrapib benefits on atherosclerotic cardiovascular outcomes in patients with the AA genotype at polymorphism rs1967309.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Clinical Trials Registration\u2014<\/jats:title>\n            <jats:p>ClinicalTrials.gov; Unique Identifiers: NCT00658515 and NCT01059682.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circgenetics.116.001405","type":"journal-article","created":{"date-parts":[[2016,7,15]],"date-time":"2016-07-15T02:23:40Z","timestamp":1468549420000},"page":"340-348","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":65,"title":["Genotype-Dependent Effects of Dalcetrapib on Cholesterol Efflux and Inflammation"],"prefix":"10.1161","volume":"9","author":[{"given":"Jean-Claude","family":"Tardif","sequence":"first","affiliation":[{"name":"From the Montreal Heart Institute (J.-C.T., D.R., M. Brodeur, M. Boul\u00e9, S.A., J.C.G., P.L.L., R.I., E.R., M.-P.D.), Universit\u00e9 de Montr\u00e9al, Faculty of Medicine (J.-C.T., J.C.G., P.L.L., R.I., E.R., M.-P.D.), Universit\u00e9 de Montr\u00e9al Beaulieu-Saucier Pharmacogenomics Center (Y.F.Z., R.F., S.P., I.M., M.-P.D.), Montreal Health Innovations Coordinating Center (MHICC) (M.-C.G.), Montreal, Canada; Linkoping University, Department of Medicine and Health, Stockholm, Sweden (A.G.O.); and Veterans Affairs..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Rhainds","sequence":"additional","affiliation":[{"name":"From the Montreal Heart Institute (J.-C.T., D.R., M. Brodeur, M. Boul\u00e9, S.A., J.C.G., P.L.L., R.I., E.R., M.-P.D.), Universit\u00e9 de Montr\u00e9al, Faculty of Medicine (J.-C.T., J.C.G., P.L.L., R.I., E.R., M.-P.D.), Universit\u00e9 de Montr\u00e9al Beaulieu-Saucier Pharmacogenomics Center (Y.F.Z., R.F., S.P., I.M., M.-P.D.), Montreal Health Innovations Coordinating Center (MHICC) (M.-C.G.), Montreal, Canada; Linkoping University, Department of Medicine and Health, Stockholm, Sweden (A.G.O.); and Veterans Affairs..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathieu","family":"Brodeur","sequence":"additional","affiliation":[{"name":"From the Montreal Heart Institute (J.-C.T., D.R., M. Brodeur, M. Boul\u00e9, S.A., J.C.G., P.L.L., R.I., E.R., M.-P.D.), Universit\u00e9 de Montr\u00e9al, Faculty of Medicine (J.-C.T., J.C.G., P.L.L., R.I., E.R., M.-P.D.), Universit\u00e9 de Montr\u00e9al Beaulieu-Saucier Pharmacogenomics Center (Y.F.Z., R.F., S.P., I.M., M.-P.D.), Montreal Health Innovations Coordinating Center (MHICC) (M.-C.G.), Montreal, Canada; Linkoping University, Department of Medicine and Health, Stockholm, Sweden (A.G.O.); and Veterans Affairs..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yassamin","family":"Feroz Zada","sequence":"additional","affiliation":[{"name":"From the Montreal Heart Institute (J.-C.T., D.R., M. Brodeur, M. Boul\u00e9, S.A., J.C.G., P.L.L., R.I., E.R., M.-P.D.), Universit\u00e9 de Montr\u00e9al, Faculty of Medicine (J.-C.T., J.C.G., P.L.L., R.I., E.R., M.-P.D.), Universit\u00e9 de Montr\u00e9al Beaulieu-Saucier Pharmacogenomics Center (Y.F.Z., R.F., S.P., I.M., M.-P.D.), Montreal Health Innovations Coordinating Center (MHICC) (M.-C.G.), Montreal, Canada; Linkoping University, Department of Medicine and Health, Stockholm, Sweden (A.G.O.); and Veterans Affairs..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ren\u00e9","family":"Fouodjio","sequence":"additional","affiliation":[{"name":"From the Montreal Heart Institute (J.-C.T., D.R., M. Brodeur, M. Boul\u00e9, S.A., J.C.G., P.L.L., R.I., E.R., M.-P.D.), Universit\u00e9 de Montr\u00e9al, Faculty of Medicine (J.-C.T., J.C.G., P.L.L., R.I., E.R., M.-P.D.), Universit\u00e9 de Montr\u00e9al Beaulieu-Saucier Pharmacogenomics Center (Y.F.Z., R.F., S.P., I.M., M.-P.D.), Montreal Health Innovations Coordinating Center (MHICC) (M.-C.G.), Montreal, Canada; Linkoping University, Department of Medicine and Health, Stockholm, Sweden (A.G.O.); and Veterans Affairs..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvie","family":"Provost","sequence":"additional","affiliation":[{"name":"From the Montreal Heart Institute (J.-C.T., D.R., M. Brodeur, M. Boul\u00e9, S.A., J.C.G., P.L.L., R.I., E.R., M.-P.D.), Universit\u00e9 de Montr\u00e9al, Faculty of Medicine (J.-C.T., J.C.G., P.L.L., R.I., E.R., M.-P.D.), Universit\u00e9 de Montr\u00e9al Beaulieu-Saucier Pharmacogenomics Center (Y.F.Z., R.F., S.P., I.M., M.-P.D.), Montreal Health Innovations Coordinating Center (MHICC) (M.-C.G.), Montreal, Canada; Linkoping University, Department of Medicine and Health, Stockholm, Sweden (A.G.O.); and Veterans Affairs..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie","family":"Boul\u00e9","sequence":"additional","affiliation":[{"name":"From the Montreal Heart Institute (J.-C.T., D.R., M. Brodeur, M. Boul\u00e9, S.A., J.C.G., P.L.L., R.I., E.R., M.-P.D.), Universit\u00e9 de Montr\u00e9al, Faculty of Medicine (J.-C.T., J.C.G., P.L.L., R.I., E.R., M.-P.D.), Universit\u00e9 de Montr\u00e9al Beaulieu-Saucier Pharmacogenomics Center (Y.F.Z., R.F., S.P., I.M., M.-P.D.), Montreal Health Innovations Coordinating Center (MHICC) (M.-C.G.), Montreal, Canada; Linkoping University, Department of Medicine and Health, Stockholm, Sweden (A.G.O.); and Veterans Affairs..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonia","family":"Alem","sequence":"additional","affiliation":[{"name":"From the Montreal Heart Institute (J.-C.T., D.R., M. Brodeur, M. Boul\u00e9, S.A., J.C.G., P.L.L., R.I., E.R., M.-P.D.), Universit\u00e9 de Montr\u00e9al, Faculty of Medicine (J.-C.T., J.C.G., P.L.L., R.I., E.R., M.-P.D.), Universit\u00e9 de Montr\u00e9al Beaulieu-Saucier Pharmacogenomics Center (Y.F.Z., R.F., S.P., I.M., M.-P.D.), Montreal Health Innovations Coordinating Center (MHICC) (M.-C.G.), Montreal, Canada; Linkoping University, Department of Medicine and Health, Stockholm, Sweden (A.G.O.); and Veterans Affairs..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean C.","family":"Gr\u00e9goire","sequence":"additional","affiliation":[{"name":"From the Montreal Heart Institute (J.-C.T., D.R., M. Brodeur, M. Boul\u00e9, S.A., J.C.G., P.L.L., R.I., E.R., M.-P.D.), Universit\u00e9 de Montr\u00e9al, Faculty of Medicine (J.-C.T., J.C.G., P.L.L., R.I., E.R., M.-P.D.), Universit\u00e9 de Montr\u00e9al Beaulieu-Saucier Pharmacogenomics Center (Y.F.Z., R.F., S.P., I.M., M.-P.D.), Montreal Health Innovations Coordinating Center (MHICC) (M.-C.G.), Montreal, Canada; Linkoping University, Department of Medicine and Health, Stockholm, Sweden (A.G.O.); and Veterans Affairs..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe L.","family":"L\u2019Allier","sequence":"additional","affiliation":[{"name":"From the Montreal Heart Institute (J.-C.T., D.R., M. Brodeur, M. Boul\u00e9, S.A., J.C.G., P.L.L., R.I., E.R., M.-P.D.), Universit\u00e9 de Montr\u00e9al, Faculty of Medicine (J.-C.T., J.C.G., P.L.L., R.I., E.R., M.-P.D.), Universit\u00e9 de Montr\u00e9al Beaulieu-Saucier Pharmacogenomics Center (Y.F.Z., R.F., S.P., I.M., M.-P.D.), Montreal Health Innovations Coordinating Center (MHICC) (M.-C.G.), Montreal, Canada; Linkoping University, Department of Medicine and Health, Stockholm, Sweden (A.G.O.); and Veterans Affairs..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reda","family":"Ibrahim","sequence":"additional","affiliation":[{"name":"From the Montreal Heart Institute (J.-C.T., D.R., M. Brodeur, M. Boul\u00e9, S.A., J.C.G., P.L.L., R.I., E.R., M.-P.D.), Universit\u00e9 de Montr\u00e9al, Faculty of Medicine (J.-C.T., J.C.G., P.L.L., R.I., E.R., M.-P.D.), Universit\u00e9 de Montr\u00e9al Beaulieu-Saucier Pharmacogenomics Center (Y.F.Z., R.F., S.P., I.M., M.-P.D.), Montreal Health Innovations Coordinating Center (MHICC) (M.-C.G.), Montreal, Canada; Linkoping University, Department of Medicine and Health, Stockholm, Sweden (A.G.O.); and Veterans Affairs..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie-Claude","family":"Guertin","sequence":"additional","affiliation":[{"name":"From the Montreal Heart Institute (J.-C.T., D.R., M. Brodeur, M. Boul\u00e9, S.A., J.C.G., P.L.L., R.I., E.R., M.-P.D.), Universit\u00e9 de Montr\u00e9al, Faculty of Medicine (J.-C.T., J.C.G., P.L.L., R.I., E.R., M.-P.D.), Universit\u00e9 de Montr\u00e9al Beaulieu-Saucier Pharmacogenomics Center (Y.F.Z., R.F., S.P., I.M., M.-P.D.), Montreal Health Innovations Coordinating Center (MHICC) (M.-C.G.), Montreal, Canada; Linkoping University, Department of Medicine and Health, Stockholm, Sweden (A.G.O.); and Veterans Affairs..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian","family":"Mongrain","sequence":"additional","affiliation":[{"name":"From the Montreal Heart Institute (J.-C.T., D.R., M. Brodeur, M. Boul\u00e9, S.A., J.C.G., P.L.L., R.I., E.R., M.-P.D.), Universit\u00e9 de Montr\u00e9al, Faculty of Medicine (J.-C.T., J.C.G., P.L.L., R.I., E.R., M.-P.D.), Universit\u00e9 de Montr\u00e9al Beaulieu-Saucier Pharmacogenomics Center (Y.F.Z., R.F., S.P., I.M., M.-P.D.), Montreal Health Innovations Coordinating Center (MHICC) (M.-C.G.), Montreal, Canada; Linkoping University, Department of Medicine and Health, Stockholm, Sweden (A.G.O.); and Veterans Affairs..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anders G.","family":"Olsson","sequence":"additional","affiliation":[{"name":"From the Montreal Heart Institute (J.-C.T., D.R., M. Brodeur, M. Boul\u00e9, S.A., J.C.G., P.L.L., R.I., E.R., M.-P.D.), Universit\u00e9 de Montr\u00e9al, Faculty of Medicine (J.-C.T., J.C.G., P.L.L., R.I., E.R., M.-P.D.), Universit\u00e9 de Montr\u00e9al Beaulieu-Saucier Pharmacogenomics Center (Y.F.Z., R.F., S.P., I.M., M.-P.D.), Montreal Health Innovations Coordinating Center (MHICC) (M.-C.G.), Montreal, Canada; Linkoping University, Department of Medicine and Health, Stockholm, Sweden (A.G.O.); and Veterans Affairs..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory G.","family":"Schwartz","sequence":"additional","affiliation":[{"name":"From the Montreal Heart Institute (J.-C.T., D.R., M. Brodeur, M. Boul\u00e9, S.A., J.C.G., P.L.L., R.I., E.R., M.-P.D.), Universit\u00e9 de Montr\u00e9al, Faculty of Medicine (J.-C.T., J.C.G., P.L.L., R.I., E.R., M.-P.D.), Universit\u00e9 de Montr\u00e9al Beaulieu-Saucier Pharmacogenomics Center (Y.F.Z., R.F., S.P., I.M., M.-P.D.), Montreal Health Innovations Coordinating Center (MHICC) (M.-C.G.), Montreal, Canada; Linkoping University, Department of Medicine and Health, Stockholm, Sweden (A.G.O.); and Veterans Affairs..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Rh\u00e9aume","sequence":"additional","affiliation":[{"name":"From the Montreal Heart Institute (J.-C.T., D.R., M. Brodeur, M. Boul\u00e9, S.A., J.C.G., P.L.L., R.I., E.R., M.-P.D.), Universit\u00e9 de Montr\u00e9al, Faculty of Medicine (J.-C.T., J.C.G., P.L.L., R.I., E.R., M.-P.D.), Universit\u00e9 de Montr\u00e9al Beaulieu-Saucier Pharmacogenomics Center (Y.F.Z., R.F., S.P., I.M., M.-P.D.), Montreal Health Innovations Coordinating Center (MHICC) (M.-C.G.), Montreal, Canada; Linkoping University, Department of Medicine and Health, Stockholm, Sweden (A.G.O.); and Veterans Affairs..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie-Pierre","family":"Dub\u00e9","sequence":"additional","affiliation":[{"name":"From the Montreal Heart Institute (J.-C.T., D.R., M. Brodeur, M. Boul\u00e9, S.A., J.C.G., P.L.L., R.I., E.R., M.-P.D.), Universit\u00e9 de Montr\u00e9al, Faculty of Medicine (J.-C.T., J.C.G., P.L.L., R.I., E.R., M.-P.D.), Universit\u00e9 de Montr\u00e9al Beaulieu-Saucier Pharmacogenomics Center (Y.F.Z., R.F., S.P., I.M., M.-P.D.), Montreal Health Innovations Coordinating Center (MHICC) (M.-C.G.), Montreal, Canada; Linkoping University, Department of Medicine and Health, Stockholm, Sweden (A.G.O.); and Veterans Affairs..."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrcardio.2015.124"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1300955"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1107579"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0706628"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1206797"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCGENETICS.114.000663"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCGENETICS.115.001037"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.2217\/fca.12.25"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1009744"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2011.1649"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000159351.95399.50"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.M059089"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri3793"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1001689"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1409065"},{"key":"e_1_3_4_17_2","unstructured":"Lilly Press Release. 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