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PLA2G7 genotype, lipoprotein-associated phospholipase A2 activity, and coronary heart disease risk in 10 494 cases and 15 624 controls of European Ancestry Casas JP; Ninio E; Panayiotou A; Palmen J; Cooper JA; Ricketts SL; Sofat R; Nicolaides AN; Corsetti JP; Fowkes FG; Tzoulaki I; Kumari M; Brunner EJ; Kivimaki M; Marmot MG; Hoffmann MM; Winkler K; Marz W; Ye S; Stirnadel HA; Boekholdt SM; Khaw KT; Humphries SE; Sandhu MS; Hingorani AD; Talmud PJCirculation 2010[Jun]; 121 (21): 2284-93BACKGROUND: 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.|1-Alkyl-2-acetylglycerophosphocholine Esterase/*metabolism[MESH]|Case-Control Studies[MESH]|Coronary Disease/enzymology/*epidemiology/genetics[MESH]|Cross-Sectional Studies[MESH]|Europe[MESH]|Genotype[MESH]|Humans[MESH]|Phospholipases A2/*genetics[MESH]|Polymorphism, Single Nucleotide/genetics[MESH]|Prospective Studies[MESH]|Risk Factors[MESH] |
