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- Title
Platelet-activating factor-acetylhydrolase and PAF-receptor gene haplotypes in relation to future cardiovascular event in patients with coronary artery disease.
- Authors
Ninio, Ewa; Tregouet, David; Carrier, Jean-Luc; Stengel, Dominique; Bickel, Christoph; Perret, Claire; Rupprecht, Hans J.; Cambien, François; Blankenberg, Stefan; Tiret, Laurence
- Abstract
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.
- Publication
Human Molecular Genetics, 2004, Vol 13, Issue 13, p1341
- ISSN
0964-6906
- Publication type
Article
- DOI
10.1093/hmg/ddh145