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...
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Published in | Human molecular genetics Vol. 13; no. 13; pp. 1341 - 1351 |
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Main Authors | , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Oxford
Oxford University Press
01.07.2004
Oxford Publishing Limited (England) |
Subjects | |
Online Access | Get full text |
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Summary: | 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. |
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Bibliography: | ark:/67375/HXZ-B76QB1SS-X To whom correspondence should be addressed at: INSERM U525, Faculté de Médecine Pitié-Salpêtrière, 91 bd de l'Hôpital, 75634 Paris cedex 13, France. Tel: +33 140779725; Fax: +33 140779768; Email: ninio@chups.jussieu.fr istex:7E4282E10B3C5CFB7622DD66901C2A61632BFAF0 local:ddh145 ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0964-6906 1460-2083 1460-2083 |
DOI: | 10.1093/hmg/ddh145 |