PLA2G7 genotype, lipoprotein-associated phospholipase A2 activity, and coronary heart disease risk in 10 494 cases and 15 624 controls of European Ancestry

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dc.contributor.authorCasas, J. P.en
dc.contributor.authorNinio, E.en
dc.contributor.authorPanayiotou, A.en
dc.contributor.authorPalmen, J.en
dc.contributor.authorCooper, J. A.en
dc.contributor.authorRicketts, S. L.en
dc.contributor.authorSofat, R.en
dc.contributor.authorNicolaides, A. N.en
dc.contributor.authorCorsetti, J. P.en
dc.contributor.authorFowkes, F. G.en
dc.contributor.authorTzoulaki, I.en
dc.contributor.authorKumari, M.en
dc.contributor.authorBrunner, E. J.en
dc.contributor.authorKivimaki, M.en
dc.contributor.authorMarmot, M. G.en
dc.contributor.authorHoffmann, M. M.en
dc.contributor.authorWinkler, K.en
dc.contributor.authorMarz, W.en
dc.contributor.authorYe, S.en
dc.contributor.authorStirnadel, H. A.en
dc.contributor.authorBoekholdt, S. M.en
dc.contributor.authorKhaw, K. T.en
dc.contributor.authorHumphries, S. E.en
dc.contributor.authorSandhu, M. S.en
dc.contributor.authorHingorani, A. D.en
dc.contributor.authorTalmud, P. J.en
dc.date.accessioned2015-11-24T18:58:20Z
dc.date.available2015-11-24T18:58:20Z
dc.identifier.issn1524-4539-
dc.identifier.urihttps://olympias.lib.uoi.gr/jspui/handle/123456789/19268
dc.rightsDefault Licence-
dc.subject1-Alkyl-2-acetylglycerophosphocholine Esterase/*metabolismen
dc.subjectCase-Control Studiesen
dc.subjectCoronary Disease/enzymology/*epidemiology/geneticsen
dc.subjectCross-Sectional Studiesen
dc.subjectEuropeen
dc.subjectGenotypeen
dc.subjectHumansen
dc.subjectPhospholipases A2/*geneticsen
dc.subjectPolymorphism, Single Nucleotide/geneticsen
dc.subjectProspective Studiesen
dc.subjectRisk Factorsen
dc.titlePLA2G7 genotype, lipoprotein-associated phospholipase A2 activity, and coronary heart disease risk in 10 494 cases and 15 624 controls of European Ancestryen
heal.abstractBACKGROUND: Higher lipoprotein-associated phospholipase A(2)(Lp-PLA2) activity is associated with increased risk of coronary heart disease (CHD), making Lp-PLA2 a potential therapeutic target. PLA2G7 variants associated with Lp-PLA2 activity could evaluate whether this relationship is causal. METHODS AND RESULTS: A meta-analysis including a total of 12 studies (5 prospective, 4 case-control, 1 case-only, and 2 cross-sectional studies; n=26 118) was undertaken to examine the association of the following: (1) Lp-PLA2 activity versus cardiovascular biomarkers and risk factors and CHD events (2 prospective studies; n=4884); (2) PLA2G7 single-nucleotide polymorphisms and Lp-PLA2 activity (3 prospective, 2 case-control, 2 cross-sectional studies; up to n=6094); and (3) PLA2G7 single-nucleotide polymorphisms and angiographic coronary artery disease (2 case-control, 1 case-only study; n=4971 cases) and CHD events (5 prospective, 2 case-control studies; n=5523). Lp-PLA2 activity correlated with several CHD risk markers. Hazard ratios for CHD events for the top versus bottom quartile of Lp-PLA2 activity were 1.61 (95% confidence interval, 1.31 to 1.99) and 1.17 (95% confidence interval, 0.91 to 1.51) after adjustment for baseline traits. Of 7 single-nucleotide polymorphisms, rs1051931 (A379V) showed the strongest association with Lp-PLA2 activity, with VV subjects having 7.2% higher activity than AAs. Genotype was not associated with risk markers, angiographic coronary disease (odds ratio, 1.03; 95% confidence interval, 0.80 to 1.32), or CHD events (odds ratio, 0.98; 95% confidence interval, 0.82 to 1.17). CONCLUSIONS: Unlike Lp-PLA2 activity, PLA2G7 variants associated with modest effects on Lp-PLA2 activity were not associated with cardiovascular risk markers, coronary atheroma, or CHD. Larger association studies, identification of single-nucleotide polymorphisms with larger effects, or randomized trials of specific Lp-PLA2 inhibitors are needed to confirm or refute a contributory role for Lp-PLA2 in CHD.en
heal.accesscampus-
heal.fullTextAvailabilityTRUE-
heal.identifier.primary10.1161/CIRCULATIONAHA.109.923383-
heal.identifier.secondaryhttp://www.ncbi.nlm.nih.gov/pubmed/20479152-
heal.identifier.secondaryhttp://circ.ahajournals.org/content/121/21/2284.full.pdf-
heal.journalNameCirculationen
heal.journalTypepeer-reviewed-
heal.languageen-
heal.publicationDate2010-
heal.recordProviderΠανεπιστήμιο Ιωαννίνων. Σχολή Επιστημών Υγείας. Τμήμα Ιατρικήςel
heal.typejournalArticle-
heal.type.elΆρθρο Περιοδικούel
heal.type.enJournal articleen

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