Platelet-activating factor-acetylhydrolase and PAF-receptor gene haplotypes in relation to future cardiovascular event in patients with coronary artery disease

• Published in: Human molecular genetics Vol. 13; no. 13; pp. 1341 - 1351
• Main Authors: Ninio, Ewa, Tregouet, David, Carrier, Jean-Luc, Stengel, Dominique, Bickel, Christoph, Perret, Claire, Rupprecht, Hans J., Cambien, François, Blankenberg, Stefan, Tiret, Laurence
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.07.2004; Oxford Publishing Limited (England)
• Subjects: 1-Alkyl-2-acetylglycerophosphocholine Esterase - blood; 1-Alkyl-2-acetylglycerophosphocholine Esterase - genetics; Biological and medical sciences; Cardiology. Vascular system; Case-Control Studies; Cell receptors; Cell structures and functions; Cohort Studies; Coronary Artery Disease - blood; Coronary Artery Disease - genetics; Coronary heart disease; Fundamental and applied biological sciences. Psychology; Genetic Predisposition to Disease; Genetics of eukaryotes. Biological and molecular evolution; Haplotypes - genetics; Heart; Humans; Lipoproteins, LDL - metabolism; Medical sciences; Miscellaneous; Molecular and cellular biology; Phenotype; Platelet Activating Factor - metabolism; Platelet Membrane Glycoproteins - genetics; Platelet Membrane Glycoproteins - metabolism; Polymorphism, Genetic; Receptors, G-Protein-Coupled - genetics; Receptors, G-Protein-Coupled - metabolism; Human; Vascular disease; Gene; Atherosclerosis; Cardiovascular disease; Genetics; Patient; Coronary heart disease; Haplotype; Platelet activating factor; Biological receptor
• ISSN: 0964-6906; 1460-2083; 1460-2083
• DOI: 10.1093/hmg/ddh145

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.