title: PLA2G7 genotype, lipoprotein-associated phospholipase A2 activity, and coronary heart disease risk in 10 494 cases and 15 624 controls of European Ancestry.
abstract: BACKGROUND
  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.
  
  
  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.
authors.affiliation: Department of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, UK. Juan.pablo-casas@lshtm.ac.uk <Juan.pablo-casas@lshtm.ac.uk>
authors.forename: Juan P
authors.initials: JP
authors.lastname: Casas
authors.forename: Ewa
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authors.lastname: Ninio
authors.forename: Andrie
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authors.lastname: Panayiotou
authors.forename: Jutta
authors.initials: J
authors.lastname: Palmen
authors.forename: Jackie A
authors.initials: JA
authors.lastname: Cooper
authors.forename: Sally L
authors.initials: SL
authors.lastname: Ricketts
authors.forename: Reecha
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authors.lastname: Sofat
authors.forename: Andrew N
authors.initials: AN
authors.lastname: Nicolaides
authors.forename: James P
authors.initials: JP
authors.lastname: Corsetti
authors.forename: F Gerry R
authors.initials: FG
authors.lastname: Fowkes
authors.forename: Ioanna
authors.initials: I
authors.lastname: Tzoulaki
authors.forename: Meena
authors.initials: M
authors.lastname: Kumari
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Brunner
authors.forename: Mika
authors.initials: M
authors.lastname: Kivimaki
authors.forename: Michael G
authors.initials: MG
authors.lastname: Marmot
authors.forename: Michael M
authors.initials: MM
authors.lastname: Hoffmann
authors.forename: Karl
authors.initials: K
authors.lastname: Winkler
authors.forename: Winfred
authors.initials: W
authors.lastname: März
authors.forename: Shu
authors.initials: S
authors.lastname: Ye
authors.forename: Heide A
authors.initials: HA
authors.lastname: Stirnadel
authors.forename: S Matthijs
authors.initials: SM
authors.lastname: Boekholdt
authors.forename: Kay-Tee
authors.initials: KT
authors.lastname: Khaw
authors.forename: Steve E
authors.initials: SE
authors.lastname: Humphries
authors.forename: Manjinder S
authors.initials: MS
authors.lastname: Sandhu
authors.forename: Aroon D
authors.initials: AD
authors.lastname: Hingorani
authors.forename: Philippa J
authors.initials: PJ
authors.lastname: Talmud
mesh_terms: D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000378:metabolism*; D016022:Case-Control Studies; D003327:Coronary Disease / Q000201:enzymology / Q000453:epidemiology* / Q000235:genetics; D003430:Cross-Sectional Studies; D005060:Europe; D005838:Genotype; D006801:Humans; D054467:Phospholipases A2 / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011446:Prospective Studies; D012307:Risk Factors
chemical_list: D054467:Phospholipases A2; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; C526684:PLA2G7 protein, human