{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T23:36:15Z","timestamp":1772580975389,"version":"3.50.1"},"reference-count":43,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Circ Cardiovasc Genet"],"published-print":{"date-parts":[[2013,2]]},"abstract":"<jats:sec>\n            <jats:title>Background\u2014<\/jats:title>\n            <jats:p>\n              Endothelial lipase is a phospholipase with activity against high-density lipoprotein. Although a small number of mutations in\n              <jats:italic>LIPG<\/jats:italic>\n              have been described, the role of\n              <jats:italic>LIPG<\/jats:italic>\n              in protection against atherosclerosis is unclear.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods and Results\u2014<\/jats:title>\n            <jats:p>\n              We identified 8 loss-of-function (LOF) mutations in\n              <jats:italic>LIPG<\/jats:italic>\n              in individuals with high-density lipoprotein cholesterol. Functional analysis confirmed that most rare mutations abolish lipase activity in vitro, indicating complete LOF, whereas 2 more common mutations N396S and R476W reduce activity by \u224850%, indicating partial LOF and implying \u224850% and \u224875% remaining endothelial lipase function in heterozygous complete LOF and partial LOF mutation carriers, respectively. complete LOF mutation carriers had significantly higher plasma high-density lipoprotein cholesterol levels compared with partial LOF mutation carriers. Apolipoprotein B-depleted serum from complete LOF carriers showed significantly enhanced cholesterol efflux acceptor capacity, whereas only trends were observed in partial LOF carriers. Carriers of\n              <jats:italic>LIPG<\/jats:italic>\n              mutations exhibited trends toward reduced coronary artery disease in 4 independent cohorts (meta-analysis odds ratio, 0.7;\n              <jats:italic>P<\/jats:italic>\n              =0.04).\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions\u2014<\/jats:title>\n            <jats:p>\n              Our data suggest that the impact of\n              <jats:italic>LIPG<\/jats:italic>\n              mutations is directly related to their effect on endothelial lipase function and support that antagonism of endothelial lipase function improves cardioprotection.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circgenetics.111.962613","type":"journal-article","created":{"date-parts":[[2012,12,16]],"date-time":"2012-12-16T01:45:13Z","timestamp":1355622313000},"page":"54-62","source":"Crossref","is-referenced-by-count":58,"title":["The Impact of Partial and Complete Loss-of-Function Mutations in Endothelial Lipase on High-Density Lipoprotein Levels and Functionality in Humans"],"prefix":"10.1161","volume":"6","author":[{"given":"Roshni R.","family":"Singaraja","sequence":"first","affiliation":[{"name":"From the Xenon Pharmaceuticals Inc., Burnaby, Canada (R.R.S., I.T., J.Mc., M.W.); Department of Vascular Medicine (S.S., K.H., G.D.-T., J.J.K.), Department of Cardiology (M.D.T.), Academic Medical Center, Amsterdam, the Netherlands; Montreal Heart Institute Research Center and Universit\u00e9 de Montr\u00e9al Facult\u00e9 de M\u00e9decine, Montr\u00e9al, Canada (M.-P.D.); Merck Research Laboratories, Rahway, NJ (J.C.-P., B.H., K.W., L.J.M., M.v.H., L.L., T.A.R.); Vascular Strategies LLC, Wynnewood, PA (H.L.C., S.J.A.);..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Suthesh","family":"Sivapalaratnam","sequence":"additional","affiliation":[{"name":"From the Xenon Pharmaceuticals Inc., Burnaby, Canada (R.R.S., I.T., J.Mc., M.W.); Department of Vascular Medicine (S.S., K.H., G.D.-T., J.J.K.), Department of Cardiology (M.D.T.), Academic Medical Center, Amsterdam, the Netherlands; Montreal Heart Institute Research Center and Universit\u00e9 de Montr\u00e9al Facult\u00e9 de M\u00e9decine, Montr\u00e9al, Canada (M.-P.D.); Merck Research Laboratories, Rahway, NJ (J.C.-P., B.H., K.W., L.J.M., M.v.H., L.L., T.A.R.); Vascular Strategies LLC, Wynnewood, PA (H.L.C., S.J.A.);..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kees","family":"Hovingh","sequence":"additional","affiliation":[{"name":"From the Xenon Pharmaceuticals Inc., Burnaby, Canada (R.R.S., I.T., J.Mc., M.W.); Department of Vascular Medicine (S.S., K.H., G.D.-T., J.J.K.), Department of Cardiology (M.D.T.), Academic Medical Center, Amsterdam, the Netherlands; Montreal Heart Institute Research Center and Universit\u00e9 de Montr\u00e9al Facult\u00e9 de M\u00e9decine, Montr\u00e9al, Canada (M.-P.D.); Merck Research Laboratories, Rahway, NJ (J.C.-P., B.H., K.W., L.J.M., M.v.H., L.L., T.A.R.); Vascular Strategies LLC, Wynnewood, PA (H.L.C., S.J.A.);..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marie-Pierre","family":"Dub\u00e9","sequence":"additional","affiliation":[{"name":"From the Xenon Pharmaceuticals Inc., Burnaby, Canada (R.R.S., I.T., J.Mc., M.W.); Department of Vascular Medicine (S.S., K.H., G.D.-T., J.J.K.), Department of Cardiology (M.D.T.), Academic Medical Center, Amsterdam, the Netherlands; Montreal Heart Institute Research Center and Universit\u00e9 de Montr\u00e9al Facult\u00e9 de M\u00e9decine, Montr\u00e9al, Canada (M.-P.D.); Merck Research Laboratories, Rahway, NJ (J.C.-P., B.H., K.W., L.J.M., M.v.H., L.L., T.A.R.); Vascular Strategies LLC, Wynnewood, PA (H.L.C., S.J.A.);..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jos\u00e9","family":"Castro-Perez","sequence":"additional","affiliation":[{"name":"From the Xenon Pharmaceuticals Inc., Burnaby, Canada (R.R.S., I.T., J.Mc., M.W.); Department of Vascular Medicine (S.S., K.H., G.D.-T., J.J.K.), Department of Cardiology (M.D.T.), Academic Medical Center, Amsterdam, the Netherlands; Montreal Heart Institute Research Center and Universit\u00e9 de Montr\u00e9al Facult\u00e9 de M\u00e9decine, Montr\u00e9al, Canada (M.-P.D.); Merck Research Laboratories, Rahway, NJ (J.C.-P., B.H., K.W., L.J.M., M.v.H., L.L., T.A.R.); Vascular Strategies LLC, Wynnewood, PA (H.L.C., S.J.A.);..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heidi L.","family":"Collins","sequence":"additional","affiliation":[{"name":"From the Xenon Pharmaceuticals Inc., Burnaby, Canada (R.R.S., I.T., J.Mc., M.W.); Department of Vascular Medicine (S.S., K.H., G.D.-T., J.J.K.), Department of Cardiology (M.D.T.), Academic Medical Center, Amsterdam, the Netherlands; Montreal Heart Institute Research Center and Universit\u00e9 de Montr\u00e9al Facult\u00e9 de M\u00e9decine, Montr\u00e9al, Canada (M.-P.D.); Merck Research Laboratories, Rahway, NJ (J.C.-P., B.H., K.W., L.J.M., M.v.H., L.L., T.A.R.); Vascular Strategies LLC, Wynnewood, PA (H.L.C., S.J.A.);..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steven J.","family":"Adelman","sequence":"additional","affiliation":[{"name":"From the Xenon Pharmaceuticals Inc., Burnaby, Canada (R.R.S., I.T., J.Mc., M.W.); Department of Vascular Medicine (S.S., K.H., G.D.-T., J.J.K.), Department of Cardiology (M.D.T.), Academic Medical Center, Amsterdam, the Netherlands; Montreal Heart Institute Research Center and Universit\u00e9 de Montr\u00e9al Facult\u00e9 de M\u00e9decine, Montr\u00e9al, Canada (M.-P.D.); Merck Research Laboratories, Rahway, NJ (J.C.-P., B.H., K.W., L.J.M., M.v.H., L.L., T.A.R.); Vascular Strategies LLC, Wynnewood, PA (H.L.C., S.J.A.);..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meliana","family":"Riwanto","sequence":"additional","affiliation":[{"name":"From the Xenon Pharmaceuticals Inc., Burnaby, Canada (R.R.S., I.T., J.Mc., M.W.); Department of Vascular Medicine (S.S., K.H., G.D.-T., J.J.K.), Department of Cardiology (M.D.T.), Academic Medical Center, Amsterdam, the Netherlands; Montreal Heart Institute Research Center and Universit\u00e9 de Montr\u00e9al Facult\u00e9 de M\u00e9decine, Montr\u00e9al, Canada (M.-P.D.); Merck Research Laboratories, Rahway, NJ (J.C.-P., B.H., K.W., L.J.M., M.v.H., L.L., T.A.R.); Vascular Strategies LLC, Wynnewood, PA (H.L.C., S.J.A.);..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jasmin","family":"Manz","sequence":"additional","affiliation":[{"name":"From the Xenon Pharmaceuticals Inc., Burnaby, Canada (R.R.S., I.T., J.Mc., M.W.); Department of Vascular Medicine (S.S., K.H., G.D.-T., J.J.K.), Department of Cardiology (M.D.T.), Academic Medical Center, Amsterdam, the Netherlands; Montreal Heart Institute Research Center and Universit\u00e9 de Montr\u00e9al Facult\u00e9 de M\u00e9decine, Montr\u00e9al, Canada (M.-P.D.); Merck Research Laboratories, Rahway, NJ (J.C.-P., B.H., K.W., L.J.M., M.v.H., L.L., T.A.R.); Vascular Strategies LLC, Wynnewood, PA (H.L.C., S.J.A.);..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brian","family":"Hubbard","sequence":"additional","affiliation":[{"name":"From the Xenon Pharmaceuticals Inc., Burnaby, Canada (R.R.S., I.T., J.Mc., M.W.); Department of Vascular Medicine (S.S., K.H., G.D.-T., J.J.K.), Department of Cardiology (M.D.T.), Academic Medical Center, Amsterdam, the Netherlands; Montreal Heart Institute Research Center and Universit\u00e9 de Montr\u00e9al Facult\u00e9 de M\u00e9decine, Montr\u00e9al, Canada (M.-P.D.); Merck Research Laboratories, Rahway, NJ (J.C.-P., B.H., K.W., L.J.M., M.v.H., L.L., T.A.R.); Vascular Strategies LLC, Wynnewood, PA (H.L.C., S.J.A.);..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ian","family":"Tietjen","sequence":"additional","affiliation":[{"name":"From the Xenon Pharmaceuticals Inc., Burnaby, Canada (R.R.S., I.T., J.Mc., M.W.); Department of Vascular Medicine (S.S., K.H., G.D.-T., J.J.K.), Department of Cardiology (M.D.T.), Academic Medical Center, Amsterdam, the Netherlands; Montreal Heart Institute Research Center and Universit\u00e9 de Montr\u00e9al Facult\u00e9 de M\u00e9decine, Montr\u00e9al, Canada (M.-P.D.); Merck Research Laboratories, Rahway, NJ (J.C.-P., B.H., K.W., L.J.M., M.v.H., L.L., T.A.R.); Vascular Strategies LLC, Wynnewood, PA (H.L.C., S.J.A.);..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenny","family":"Wong","sequence":"additional","affiliation":[{"name":"From the Xenon Pharmaceuticals Inc., Burnaby, Canada (R.R.S., I.T., J.Mc., M.W.); Department of Vascular Medicine (S.S., K.H., G.D.-T., J.J.K.), Department of Cardiology (M.D.T.), Academic Medical Center, Amsterdam, the Netherlands; Montreal Heart Institute Research Center and Universit\u00e9 de Montr\u00e9al Facult\u00e9 de M\u00e9decine, Montr\u00e9al, Canada (M.-P.D.); Merck Research Laboratories, Rahway, NJ (J.C.-P., B.H., K.W., L.J.M., M.v.H., L.L., T.A.R.); Vascular Strategies LLC, Wynnewood, PA (H.L.C., S.J.A.);..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lyndon J.","family":"Mitnaul","sequence":"additional","affiliation":[{"name":"From the Xenon Pharmaceuticals Inc., Burnaby, Canada (R.R.S., I.T., J.Mc., M.W.); Department of Vascular Medicine (S.S., K.H., G.D.-T., J.J.K.), Department of Cardiology (M.D.T.), Academic Medical Center, Amsterdam, the Netherlands; Montreal Heart Institute Research Center and Universit\u00e9 de Montr\u00e9al Facult\u00e9 de M\u00e9decine, Montr\u00e9al, Canada (M.-P.D.); Merck Research Laboratories, Rahway, NJ (J.C.-P., B.H., K.W., L.J.M., M.v.H., L.L., T.A.R.); Vascular Strategies LLC, Wynnewood, PA (H.L.C., S.J.A.);..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Margaret","family":"van Heek","sequence":"additional","affiliation":[{"name":"From the Xenon Pharmaceuticals Inc., Burnaby, Canada (R.R.S., I.T., J.Mc., M.W.); Department of Vascular Medicine (S.S., K.H., G.D.-T., J.J.K.), Department of Cardiology (M.D.T.), Academic Medical Center, Amsterdam, the Netherlands; Montreal Heart Institute Research Center and Universit\u00e9 de Montr\u00e9al Facult\u00e9 de M\u00e9decine, Montr\u00e9al, Canada (M.-P.D.); Merck Research Laboratories, Rahway, NJ (J.C.-P., B.H., K.W., L.J.M., M.v.H., L.L., T.A.R.); Vascular Strategies LLC, Wynnewood, PA (H.L.C., S.J.A.);..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Linus","family":"Lin","sequence":"additional","affiliation":[{"name":"From the Xenon Pharmaceuticals Inc., Burnaby, Canada (R.R.S., I.T., J.Mc., M.W.); Department of Vascular Medicine (S.S., K.H., G.D.-T., J.J.K.), Department of Cardiology (M.D.T.), Academic Medical Center, Amsterdam, the Netherlands; Montreal Heart Institute Research Center and Universit\u00e9 de Montr\u00e9al Facult\u00e9 de M\u00e9decine, Montr\u00e9al, Canada (M.-P.D.); Merck Research Laboratories, Rahway, NJ (J.C.-P., B.H., K.W., L.J.M., M.v.H., L.L., T.A.R.); Vascular Strategies LLC, Wynnewood, PA (H.L.C., S.J.A.);..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas A.","family":"Roddy","sequence":"additional","affiliation":[{"name":"From the Xenon Pharmaceuticals Inc., Burnaby, Canada (R.R.S., I.T., J.Mc., M.W.); Department of Vascular Medicine (S.S., K.H., G.D.-T., J.J.K.), Department of Cardiology (M.D.T.), Academic Medical Center, Amsterdam, the Netherlands; Montreal Heart Institute Research Center and Universit\u00e9 de Montr\u00e9al Facult\u00e9 de M\u00e9decine, Montr\u00e9al, Canada (M.-P.D.); Merck Research Laboratories, Rahway, NJ (J.C.-P., B.H., K.W., L.J.M., M.v.H., L.L., T.A.R.); Vascular Strategies LLC, Wynnewood, PA (H.L.C., S.J.A.);..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jason","family":"McEwen","sequence":"additional","affiliation":[{"name":"From the Xenon Pharmaceuticals Inc., Burnaby, Canada (R.R.S., I.T., J.Mc., M.W.); Department of Vascular Medicine (S.S., K.H., G.D.-T., J.J.K.), Department of Cardiology (M.D.T.), Academic Medical Center, Amsterdam, the Netherlands; Montreal Heart Institute Research Center and Universit\u00e9 de Montr\u00e9al Facult\u00e9 de M\u00e9decine, Montr\u00e9al, Canada (M.-P.D.); Merck Research Laboratories, Rahway, NJ (J.C.-P., B.H., K.W., L.J.M., M.v.H., L.L., T.A.R.); Vascular Strategies LLC, Wynnewood, PA (H.L.C., S.J.A.);..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Geesje","family":"Dallinge-Thie","sequence":"additional","affiliation":[{"name":"From the Xenon Pharmaceuticals Inc., Burnaby, Canada (R.R.S., I.T., J.Mc., M.W.); Department of Vascular Medicine (S.S., K.H., G.D.-T., J.J.K.), Department of Cardiology (M.D.T.), Academic Medical Center, Amsterdam, the Netherlands; Montreal Heart Institute Research Center and Universit\u00e9 de Montr\u00e9al Facult\u00e9 de M\u00e9decine, Montr\u00e9al, Canada (M.-P.D.); Merck Research Laboratories, Rahway, NJ (J.C.-P., B.H., K.W., L.J.M., M.v.H., L.L., T.A.R.); Vascular Strategies LLC, Wynnewood, PA (H.L.C., S.J.A.);..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leonie","family":"van Vark-van der Zee","sequence":"additional","affiliation":[{"name":"From the Xenon Pharmaceuticals Inc., Burnaby, Canada (R.R.S., I.T., J.Mc., M.W.); Department of Vascular Medicine (S.S., K.H., G.D.-T., J.J.K.), Department of Cardiology (M.D.T.), Academic Medical Center, Amsterdam, the Netherlands; Montreal Heart Institute Research Center and Universit\u00e9 de Montr\u00e9al Facult\u00e9 de M\u00e9decine, Montr\u00e9al, Canada (M.-P.D.); Merck Research Laboratories, Rahway, NJ (J.C.-P., B.H., K.W., L.J.M., M.v.H., L.L., T.A.R.); Vascular Strategies LLC, Wynnewood, PA (H.L.C., S.J.A.);..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Germaine","family":"Verwoert","sequence":"additional","affiliation":[{"name":"From the Xenon Pharmaceuticals Inc., Burnaby, Canada (R.R.S., I.T., J.Mc., M.W.); Department of Vascular Medicine (S.S., K.H., G.D.-T., J.J.K.), Department of Cardiology (M.D.T.), Academic Medical Center, Amsterdam, the Netherlands; Montreal Heart Institute Research Center and Universit\u00e9 de Montr\u00e9al Facult\u00e9 de M\u00e9decine, Montr\u00e9al, Canada (M.-P.D.); Merck Research Laboratories, Rahway, NJ (J.C.-P., B.H., K.W., L.J.M., M.v.H., L.L., T.A.R.); Vascular Strategies LLC, Wynnewood, PA (H.L.C., S.J.A.);..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Winther","sequence":"additional","affiliation":[{"name":"From the Xenon Pharmaceuticals Inc., Burnaby, Canada (R.R.S., I.T., J.Mc., M.W.); Department of Vascular Medicine (S.S., K.H., G.D.-T., J.J.K.), Department of Cardiology (M.D.T.), Academic Medical Center, Amsterdam, the Netherlands; Montreal Heart Institute Research Center and Universit\u00e9 de Montr\u00e9al Facult\u00e9 de M\u00e9decine, Montr\u00e9al, Canada (M.-P.D.); Merck Research Laboratories, Rahway, NJ (J.C.-P., B.H., K.W., L.J.M., M.v.H., L.L., T.A.R.); Vascular Strategies LLC, Wynnewood, PA (H.L.C., S.J.A.);..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cornelia","family":"van Duijn","sequence":"additional","affiliation":[{"name":"From the Xenon Pharmaceuticals Inc., Burnaby, Canada (R.R.S., I.T., J.Mc., M.W.); Department of Vascular Medicine (S.S., K.H., G.D.-T., J.J.K.), Department of Cardiology (M.D.T.), Academic Medical Center, Amsterdam, the Netherlands; Montreal Heart Institute Research Center and Universit\u00e9 de Montr\u00e9al Facult\u00e9 de M\u00e9decine, Montr\u00e9al, Canada (M.-P.D.); Merck Research Laboratories, Rahway, NJ (J.C.-P., B.H., K.W., L.J.M., M.v.H., L.L., T.A.R.); 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