{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T11:59:22Z","timestamp":1782129562722,"version":"3.54.5"},"reference-count":48,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","content-domain":{"domain":["ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circ Cardiovasc Genet"],"published-print":{"date-parts":[[2016,6]]},"abstract":"<jats:sec>\n            <jats:title>Background\u2014<\/jats:title>\n            <jats:p>\n              Plasma triglyceride levels have been implicated in atherosclerosis and coronary heart disease. Apolipoprotein C-III (APOC3) plays a key role in the hydrolysis of triglyceride-rich lipoproteins to remnant particles by lipoprotein lipase (LPL) and their uptake by the liver. A rare variant in\n              <jats:italic>APOC3<\/jats:italic>\n              (rs138326449) has been associated with triglyceride, very low\u2013density lipoprotein, and high-density lipoprotein levels, as well as risk of coronary heart disease. We aimed to characterize the impact of this locus across a broad set of mainly lipids-focused metabolic measures.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods and Results\u2014<\/jats:title>\n            <jats:p>\n              A high-throughput serum nuclear magnetic resonance metabolomics platform was used to quantify 225 metabolic measures in 13\u2009285 participants from 2 European population cohorts. We analyzed the effect of the\n              <jats:italic>APOC3<\/jats:italic>\n              variant on the metabolic measures and used the common\n              <jats:italic>LPL<\/jats:italic>\n              (rs12678919) polymorphism to test for LPL-independent effects. Eighty-one metabolic measures showed evidence of association with\n              <jats:italic>APOC3<\/jats:italic>\n              (rs138326449). In addition to previously reported triglyceride and high-density lipoprotein associations, the variant was also associated with very low\u2013density lipoprotein and high-density lipoprotein composition measures, other cholesterol measures, and fatty acids. Comparison of the\n              <jats:italic>APOC3<\/jats:italic>\n              and\n              <jats:italic>LPL<\/jats:italic>\n              associations revealed that\n              <jats:italic>APOC3<\/jats:italic>\n              association results for medium and very large very low\u2013density lipoprotein composition are unlikely to be solely predictable by the action of APOC3 through LPL.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions\u2014<\/jats:title>\n            <jats:p>\n              We characterized the effects of the rare\n              <jats:italic>APOC3<\/jats:italic>\n              (rs138326449) loss of function mutation in lipoprotein metabolism, as well as the effects of\n              <jats:italic>LPL<\/jats:italic>\n              (rs12678919). Our results improve our understanding of the role of\n              <jats:italic>APOC3<\/jats:italic>\n              in triglyceride metabolism, its\n              <jats:italic>LPL<\/jats:italic>\n              independent action, and the complex and correlated nature of human metabolites.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circgenetics.115.001302","type":"journal-article","created":{"date-parts":[[2016,4,26]],"date-time":"2016-04-26T04:23:55Z","timestamp":1461644635000},"page":"231-239","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":27,"title":["Metabolic Characterization of a Rare Genetic Variation Within\n            <i>APOC3<\/i>\n            and Its Lipoprotein Lipase\u2013Independent Effects"],"prefix":"10.1161","volume":"9","author":[{"given":"Fotios","family":"Drenos","sequence":"first","affiliation":[{"name":"From the MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol (F.D., G.D.S., M.A.-K., D.A.L., T.R.G., N.J.T.); Institute of Cardiovascular Science, University College London, London, United Kingdom (F.D., C.D., J.-P.C.); Computational Medicine, Faculty of Medicine, University of Oulu &amp; Biocenter Oulu, Oulu (M.A.-K., J.K., P.W., P.S., A.J.K.); NMR Metabolomics Laboratory, School of Pharmacy, University of Eastern Finland, Kuopio (M.A.-K., J.K...."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George","family":"Davey Smith","sequence":"additional","affiliation":[{"name":"From the MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol (F.D., G.D.S., M.A.-K., D.A.L., T.R.G., N.J.T.); Institute of Cardiovascular Science, University College London, London, United Kingdom (F.D., C.D., J.-P.C.); Computational Medicine, Faculty of Medicine, University of Oulu &amp; Biocenter Oulu, Oulu (M.A.-K., J.K., P.W., P.S., A.J.K.); NMR Metabolomics Laboratory, School of Pharmacy, University of Eastern Finland, Kuopio (M.A.-K., J.K...."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mika","family":"Ala-Korpela","sequence":"additional","affiliation":[{"name":"From the MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol (F.D., G.D.S., M.A.-K., D.A.L., T.R.G., N.J.T.); Institute of Cardiovascular Science, University College London, London, United Kingdom (F.D., C.D., J.-P.C.); Computational Medicine, Faculty of Medicine, University of Oulu &amp; Biocenter Oulu, Oulu (M.A.-K., J.K., P.W., P.S., A.J.K.); NMR Metabolomics Laboratory, School of Pharmacy, University of Eastern Finland, Kuopio (M.A.-K., J.K...."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes","family":"Kettunen","sequence":"additional","affiliation":[{"name":"From the MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol (F.D., G.D.S., M.A.-K., D.A.L., T.R.G., N.J.T.); Institute of Cardiovascular Science, University College London, London, United Kingdom (F.D., C.D., J.-P.C.); Computational Medicine, Faculty of Medicine, University of Oulu &amp; Biocenter Oulu, Oulu (M.A.-K., J.K., P.W., P.S., A.J.K.); NMR Metabolomics Laboratory, School of Pharmacy, University of Eastern Finland, Kuopio (M.A.-K., J.K...."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"W\u00fcrtz","sequence":"additional","affiliation":[{"name":"From the MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol (F.D., G.D.S., M.A.-K., D.A.L., T.R.G., N.J.T.); Institute of Cardiovascular Science, University College London, London, United Kingdom (F.D., C.D., J.-P.C.); Computational Medicine, Faculty of Medicine, University of Oulu &amp; Biocenter Oulu, Oulu (M.A.-K., J.K., P.W., P.S., A.J.K.); NMR Metabolomics Laboratory, School of Pharmacy, University of Eastern Finland, Kuopio (M.A.-K., J.K...."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pasi","family":"Soininen","sequence":"additional","affiliation":[{"name":"From the MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol (F.D., G.D.S., M.A.-K., D.A.L., T.R.G., N.J.T.); Institute of Cardiovascular Science, University College London, London, United Kingdom (F.D., C.D., J.-P.C.); Computational Medicine, Faculty of Medicine, University of Oulu &amp; Biocenter Oulu, Oulu (M.A.-K., J.K., P.W., P.S., A.J.K.); NMR Metabolomics Laboratory, School of Pharmacy, University of Eastern Finland, Kuopio (M.A.-K., J.K...."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antti J.","family":"Kangas","sequence":"additional","affiliation":[{"name":"From the MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol (F.D., G.D.S., M.A.-K., D.A.L., T.R.G., N.J.T.); Institute of Cardiovascular Science, University College London, London, United Kingdom (F.D., C.D., J.-P.C.); Computational Medicine, Faculty of Medicine, University of Oulu &amp; Biocenter Oulu, Oulu (M.A.-K., J.K., P.W., P.S., A.J.K.); NMR Metabolomics Laboratory, School of Pharmacy, University of Eastern Finland, Kuopio (M.A.-K., J.K...."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Dale","sequence":"additional","affiliation":[{"name":"From the MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol (F.D., G.D.S., M.A.-K., D.A.L., T.R.G., N.J.T.); Institute of Cardiovascular Science, University College London, London, United Kingdom (F.D., C.D., J.-P.C.); Computational Medicine, Faculty of Medicine, University of Oulu &amp; Biocenter Oulu, Oulu (M.A.-K., J.K., P.W., P.S., A.J.K.); NMR Metabolomics Laboratory, School of Pharmacy, University of Eastern Finland, Kuopio (M.A.-K., J.K...."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Debbie A.","family":"Lawlor","sequence":"additional","affiliation":[{"name":"From the MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol (F.D., G.D.S., M.A.-K., D.A.L., T.R.G., N.J.T.); Institute of Cardiovascular Science, University College London, London, United Kingdom (F.D., C.D., J.-P.C.); Computational Medicine, Faculty of Medicine, University of Oulu &amp; Biocenter Oulu, Oulu (M.A.-K., J.K., P.W., P.S., A.J.K.); NMR Metabolomics Laboratory, School of Pharmacy, University of Eastern Finland, Kuopio (M.A.-K., J.K...."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom R.","family":"Gaunt","sequence":"additional","affiliation":[{"name":"From the MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol (F.D., G.D.S., M.A.-K., D.A.L., T.R.G., N.J.T.); Institute of Cardiovascular Science, University College London, London, United Kingdom (F.D., C.D., J.-P.C.); Computational Medicine, Faculty of Medicine, University of Oulu &amp; Biocenter Oulu, Oulu (M.A.-K., J.K., P.W., P.S., A.J.K.); NMR Metabolomics Laboratory, School of Pharmacy, University of Eastern Finland, Kuopio (M.A.-K., J.K...."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan-Pablo","family":"Casas","sequence":"additional","affiliation":[{"name":"From the MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol (F.D., G.D.S., M.A.-K., D.A.L., T.R.G., N.J.T.); 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