{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T16:29:37Z","timestamp":1768321777462,"version":"3.49.0"},"reference-count":34,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Circ Cardiovasc Genet"],"published-print":{"date-parts":[[2012,12]]},"abstract":"<jats:sec>\n            <jats:title>Background\u2014<\/jats:title>\n            <jats:p>\n              Lipoprotein-associated phospholipase A\n              <jats:sub>2<\/jats:sub>\n              (Lp-PLA\n              <jats:sub>2<\/jats:sub>\n              ) is a proinflammatory enzyme bound to low-density lipoprotein cholesterol and other circulating lipoproteins. Two measures of Lp-PLA\n              <jats:sub>2<\/jats:sub>\n              , mass and activity, are associated with increased cardiovascular risk. Data are sparse regarding genetic determinants of Lp-PLA\n              <jats:sub>2<\/jats:sub>\n              mass and activity, and no prior data are available addressing genetic determinants of statin-induced changes for this proinflammatory biomarker.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>\n              <jats:italic>Methods and Results<\/jats:italic>\n              \u2014\n            <\/jats:title>\n            <jats:p>\n              We performed a genome-wide association study of Lp-PLA\n              <jats:sub>2<\/jats:sub>\n              mass and activity at baseline and after 12 months of rosuvastatin therapy (20 mg\/d) among 6851 participants of European ancestry from the Justification for Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) and performed replication in a meta-analysis of 13 664 participants from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium. Novel associations were identified and replicated at\n              <jats:italic>MS4A4E<\/jats:italic>\n              and\n              <jats:italic>TMEM49<\/jats:italic>\n              for baseline Lp-PLA\n              <jats:sub>2<\/jats:sub>\n              activity with genome-wide significant joint\n              <jats:italic>P<\/jats:italic>\n              values (\n              <jats:italic>P<\/jats:italic>\n              =2.0\u00d710\n              <jats:sup>\u221211<\/jats:sup>\n              and\n              <jats:italic>P<\/jats:italic>\n              =2.9\u00d710\n              <jats:sup>\u22129<\/jats:sup>\n              , respectively). In addition, genome-wide associations (\n              <jats:italic>P<\/jats:italic>\n              &lt;5\u00d710\n              <jats:sup>\u22128<\/jats:sup>\n              ) were identified and replicated for baseline Lp-PLA\n              <jats:sub>2<\/jats:sub>\n              mass at\n              <jats:italic>CETP<\/jats:italic>\n              and for Lp-PLA\n              <jats:sub>2<\/jats:sub>\n              activity at the\n              <jats:italic>APOC1-APOE<\/jats:italic>\n              and\n              <jats:italic>PLA2G7<\/jats:italic>\n              loci. Among 2673 statin-allocated participants, both Lp-PLA\n              <jats:sub>2<\/jats:sub>\n              mass and activity were reduced by &gt;30% and low-density lipoprotein cholesterol by 50% after 12 months of statin therapy (\n              <jats:italic>P<\/jats:italic>\n              &lt;0.001 for both). Variants in\n              <jats:italic>ABCG2<\/jats:italic>\n              and\n              <jats:italic>LPA<\/jats:italic>\n              were associated with change in statin-induced Lp-PLA\n              <jats:sub>2<\/jats:sub>\n              activity at genome-wide significance but were substantially attenuated after adjustment for statin-induced changes in lipid levels.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions\u2014<\/jats:title>\n            <jats:p>\n              Genome-wide significant associations at\n              <jats:italic>MS4A4E<\/jats:italic>\n              and\n              <jats:italic>TMEM49<\/jats:italic>\n              may reflect novel influences on circulating levels of Lp-PLA\n              <jats:sub>2<\/jats:sub>\n              activity. In addition, genome-wide significant associations with rosuvastatin-induced change in Lp-PLA\n              <jats:sub>2<\/jats:sub>\n              activity were observed in\n              <jats:italic>ABCG2<\/jats:italic>\n              and\n              <jats:italic>LPA<\/jats:italic>\n              , likely because of their impact on statin-induced low-density lipoprotein cholesterol lowering.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circgenetics.112.963314","type":"journal-article","created":{"date-parts":[[2012,11,3]],"date-time":"2012-11-03T00:24:35Z","timestamp":1351902275000},"page":"676-685","source":"Crossref","is-referenced-by-count":35,"title":["Genome-Wide Association Study Evaluating Lipoprotein-Associated Phospholipase A\n            <sub>2<\/sub>\n            Mass and Activity at Baseline and After Rosuvastatin Therapy"],"prefix":"10.1161","volume":"5","author":[{"given":"Audrey Y.","family":"Chu","sequence":"first","affiliation":[{"name":"From the Center for Cardiovascular Disease Prevention, the Division of Preventive Medicine (A.Y.C., F.G., D.I.C., P.M.R.), Division of Genetics (D.I.C.), and Division of Cardiology (P.M.R.), Brigham and Women\u2019s Hospital, Boston, MA; Helmholtz ZentrumM\u00fcnchen, German Research Center for Environmental Health, Research Unit of Molecular Epidemiology, Neuherberg, Germany (H.G.); National Heart, Lung, and Blood Institute\u2019s and Boston University\u2019s Framingham Heart Study, Framingham, MA (J.D.); Department..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Franco","family":"Guilianini","sequence":"additional","affiliation":[{"name":"From the Center for Cardiovascular Disease Prevention, the Division of Preventive Medicine (A.Y.C., F.G., D.I.C., P.M.R.), Division of Genetics (D.I.C.), and Division of Cardiology (P.M.R.), Brigham and Women\u2019s Hospital, Boston, MA; Helmholtz ZentrumM\u00fcnchen, German Research Center for Environmental Health, Research Unit of Molecular Epidemiology, Neuherberg, Germany (H.G.); National Heart, Lung, and Blood Institute\u2019s and Boston University\u2019s Framingham Heart Study, Framingham, MA (J.D.); Department..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Harald","family":"Grallert","sequence":"additional","affiliation":[{"name":"From the Center for Cardiovascular Disease Prevention, the Division of Preventive Medicine (A.Y.C., F.G., D.I.C., P.M.R.), Division of Genetics (D.I.C.), and Division of Cardiology (P.M.R.), Brigham and Women\u2019s Hospital, Boston, MA; Helmholtz ZentrumM\u00fcnchen, German Research Center for Environmental Health, Research Unit of Molecular Epidemiology, Neuherberg, Germany (H.G.); National Heart, Lung, and Blood Institute\u2019s and Boston University\u2019s Framingham Heart Study, Framingham, MA (J.D.); Department..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jos\u00e9e","family":"Dupuis","sequence":"additional","affiliation":[{"name":"From the Center for Cardiovascular Disease Prevention, the Division of Preventive Medicine (A.Y.C., F.G., D.I.C., P.M.R.), Division of Genetics (D.I.C.), and Division of Cardiology (P.M.R.), Brigham and Women\u2019s Hospital, Boston, MA; Helmholtz ZentrumM\u00fcnchen, German Research Center for Environmental Health, Research Unit of Molecular Epidemiology, Neuherberg, Germany (H.G.); National Heart, Lung, and Blood Institute\u2019s and Boston University\u2019s Framingham Heart Study, Framingham, MA (J.D.); Department..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christie M.","family":"Ballantyne","sequence":"additional","affiliation":[{"name":"From the Center for Cardiovascular Disease Prevention, the Division of Preventive Medicine (A.Y.C., F.G., D.I.C., P.M.R.), Division of Genetics (D.I.C.), and Division of Cardiology (P.M.R.), Brigham and Women\u2019s Hospital, Boston, MA; Helmholtz ZentrumM\u00fcnchen, German Research Center for Environmental Health, Research Unit of Molecular Epidemiology, Neuherberg, Germany (H.G.); National Heart, Lung, and Blood Institute\u2019s and Boston University\u2019s Framingham Heart Study, Framingham, MA (J.D.); Department..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bryan J.","family":"Barratt","sequence":"additional","affiliation":[{"name":"From the Center for Cardiovascular Disease Prevention, the Division of Preventive Medicine (A.Y.C., F.G., D.I.C., P.M.R.), Division of Genetics (D.I.C.), and Division of Cardiology (P.M.R.), Brigham and Women\u2019s Hospital, Boston, MA; Helmholtz ZentrumM\u00fcnchen, German Research Center for Environmental Health, Research Unit of Molecular Epidemiology, Neuherberg, Germany (H.G.); National Heart, Lung, and Blood Institute\u2019s and Boston University\u2019s Framingham Heart Study, Framingham, MA (J.D.); Department..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fredrik","family":"Nyberg","sequence":"additional","affiliation":[{"name":"From the Center for Cardiovascular Disease Prevention, the Division of Preventive Medicine (A.Y.C., F.G., D.I.C., P.M.R.), Division of Genetics (D.I.C.), and Division of Cardiology (P.M.R.), Brigham and Women\u2019s Hospital, Boston, MA; Helmholtz ZentrumM\u00fcnchen, German Research Center for Environmental Health, Research Unit of Molecular Epidemiology, Neuherberg, Germany (H.G.); National Heart, Lung, and Blood Institute\u2019s and Boston University\u2019s Framingham Heart Study, Framingham, MA (J.D.); Department..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel I.","family":"Chasman","sequence":"additional","affiliation":[{"name":"From the Center for Cardiovascular Disease Prevention, the Division of Preventive Medicine (A.Y.C., F.G., D.I.C., P.M.R.), Division of Genetics (D.I.C.), and Division of Cardiology (P.M.R.), Brigham and Women\u2019s Hospital, Boston, MA; Helmholtz ZentrumM\u00fcnchen, German Research Center for Environmental Health, Research Unit of Molecular Epidemiology, Neuherberg, Germany (H.G.); National Heart, Lung, and Blood Institute\u2019s and Boston University\u2019s Framingham Heart Study, Framingham, MA (J.D.); Department..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul M.","family":"Ridker","sequence":"additional","affiliation":[{"name":"From the Center for Cardiovascular Disease Prevention, the Division of Preventive Medicine (A.Y.C., F.G., D.I.C., P.M.R.), Division of Genetics (D.I.C.), and Division of Cardiology (P.M.R.), Brigham and Women\u2019s Hospital, Boston, MA; Helmholtz ZentrumM\u00fcnchen, German Research Center for Environmental Health, Research Unit of Molecular Epidemiology, Neuherberg, Germany (H.G.); National Heart, Lung, and Blood Institute\u2019s and Boston University\u2019s Framingham Heart Study, Framingham, MA (J.D.); Department..."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(10)60319-4"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.19.12.2909"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.atv.0000244681.72738.bc"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.1870"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0018208"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-008-0587-4"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.thromres.2010.09.009"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1161\/circulationaha.109.923383"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2008.10.030"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2275(20)34942-7"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2008.08.045"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddh145"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2008.03216.x"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1000928"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehr372"},{"key":"e_1_3_4_17_2","unstructured":"The stabilization of atherosclerotic plaque by initation of darapladib therapy trial (STABILITY). http:\/\/clinicaltrials.gov\/ct2\/show\/nct00799903 Accessed August 24 2012."},{"key":"e_1_3_4_18_2","unstructured":"The stabilization of plaques using darapladib-thromboysis in myocardial infarction 52 Trial (SOLID-TIMI). http:\/\/clinicaltrials.gov\/ct2\/show\/NCT01000727. 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