Platelet-activating factor-acetylhydrolase and PAF-receptor gene haplotypes in relation to future cardiovascular event in patients with coronary artery disease.
Oxidation of low density lipoproteins is an initial step of atherogenesis that generates pro-inflammatory phospholipids, including platelet-activating factor (PAF) and its analogs. PAF is degraded by PAF-acetylhydrolase (PAF-AH), a circulating enzyme having both pro- and anti-inflammatory activities. PAF-AH activity has been postulated to be a risk factor for coronary artery disease (CAD); however, whether PAF-AH has a causal role or is simply a marker of risk is unclear. The aim of this study was to relate the variability of the genes encoding PAF-AH (PLA2G7) and the PAF-receptor (PTAFR) to the risk of CAD and its complications. All polymorphisms located in putatively functional regions were investigated in a prospective cohort of CAD patients (n = 1314) and a group of healthy controls (n = 485). The whole gene variability was investigated in relation to case-control status, prospective cardiovascular outcome and plasma PAF-AH levels by means of haplotype analyses. All analyses indicated an effect of the PLA2G7/A379V polymorphism independent of the other polymorphisms. The V379 allele was less frequent in CAD patients than in controls and was associated with a lower risk of future cardiovascular events, suggesting that this allele might be protective against the development of CAD. The V379 allele was also associated with a weak increase of plasma PAF-AH activity that was unlikely to explain the protective effect of the allele on risk. A more likely interpretation is that the A379V polymorphism might modify the enzyme function towards a more anti-atherogenic form. Polymorphisms of the PTAFR gene were not related to any phenotype.
Ninio
Ewa
E
INSERM U525/IFR14 Coeur Muscle Vaisseaux and Université PM Curie/Faculté de Médecine Pitié-Salpêtriére, Paris, France. ninio@chups.jussieu.fr
Tregouet
David
D
Carrier
Jean-Luc
JL
Stengel
Dominique
D
Bickel
Christoph
C
Perret
Claire
C
Rupprecht
Hans J
HJ
Cambien
François
F
Blankenberg
Stefan
S
Tiret
Laurence
L
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000097:blood / Q000235:genetics*; D016022:Case-Control Studies; D015331:Cohort Studies; D003324:Coronary Artery Disease / Q000097:blood / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism; D010641:Phenotype; D010972:Platelet Activating Factor / Q000378:metabolism; D010980:Platelet Membrane Glycoproteins / Q000235:genetics* / Q000378:metabolism; D011110:Polymorphism, Genetic; D043562:Receptors, G-Protein-Coupled / Q000235:genetics* / Q000378:metabolism
D008077:Lipoproteins, LDL; D010972:Platelet Activating Factor; D010980:Platelet Membrane Glycoproteins; D043562:Receptors, G-Protein-Coupled; C039351:platelet activating factor receptor; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase