Title : Platelet-activating factor-acetylhydrolase and PAF-receptor gene haplotypes in relation to future cardiovascular event in patients with coronary artery disease - Ninio_2004_Hum.Mol.Genet_13_1341 |
Author(s) : Ninio E , Tregouet D , Carrier JL , Stengel D , Bickel C , Perret C , Rupprecht HJ , Cambien F , Blankenberg S , Tiret L |
Ref : Hum Mol Genet , 13 :1341 , 2004 |
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. |
PubMedSearch : Ninio_2004_Hum.Mol.Genet_13_1341 |
PubMedID: 15115767 |
Gene_locus related to this paper: human-PLA2G7 |
Ninio E, Tregouet D, Carrier JL, Stengel D, Bickel C, Perret C, Rupprecht HJ, Cambien F, Blankenberg S, Tiret L (2004)
Platelet-activating factor-acetylhydrolase and PAF-receptor gene haplotypes in relation to future cardiovascular event in patients with coronary artery disease
Hum Mol Genet
13 :1341
Ninio E, Tregouet D, Carrier JL, Stengel D, Bickel C, Perret C, Rupprecht HJ, Cambien F, Blankenberg S, Tiret L (2004)
Hum Mol Genet
13 :1341