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Title: PLA2G7 Genotype, lipoprotein-associated phospholipase A2 activity, and coronary heart disease risk in 10 494 cases and 15 624 controls of european ancestry
Authors: Casas, Juan Pablo 
Ninio, Ewa 
Panayiotou, Andrie G. 
Palmen, Jutta A. 
Cooper, Jackie A. 
Ricketts, Sally L. 
Sofat, Reecha 
Nicolaides, Andrew N. 
Corsetti, James P. 
Fowkes, Francis Gerald R 
Tzoulaki, Ioanna 
Kumari, Meena 
Brunner, Eric John 
Kivimaki, Mika 
Marmot, Michael Gideon Ideon 
Hoffmann, Michael Marcus 
Winkler, Karl 
Marz, Winfred 
Ye, Shu 
Stirnadel, Heide A. 
Khaw, Kay Tee T 
Humphries, Steve Eric 
Sandhu, Manjinder S. 
Hingorani, Aroon D. 
Talmud, Philippa J. 
Major Field of Science: Medical and Health Sciences
Field Category: Clinical Medicine
Keywords: Epidemiology;Genetics;Mendelian randomization analysis;Risk factors
Issue Date: 1-Jun-2010
Source: Circulation, 2010, vol. 121, no. 21, pp. 2284-2293
Volume: 121
Issue: 21
Start page: 2284
End page: 2293
Journal: Circulation 
Abstract: BACKGROUND-: Higher lipoprotein-associated phospholipase A2(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.
ISSN: 15244539
DOI: 10.1161/CIRCULATIONAHA.109.923383
Rights: © American Heart Association
Type: Article
Affiliation : London School of Hygiene and Tropical Medicine 
University College London 
Pierre et Marie Curie University 
University of Cyprus 
University of Cambridge 
Wellcome Trust Sanger Institute 
Cyprus Cardiovascular Disease and Educational Research Trust 
Imperial College London 
University of Rochester 
The University of Edinburgh 
Universitätsklinikum Freiburg 
Synlab Medizinisches Versorgungszentrum für Labordiagnostik Heidelberg 
Queen Mary University of London 
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