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

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.

Protective role of Lipoprotein-Associated Phospholipase A2 Gene (A379V) Polymorphism against Myocardial Infarction among Egyptians

“…In agreement with our study, Ninio e et al, 22 Abuzeid AM et al, 23 and ling lC et al, 24 reported that the homozygous (tt) and heterozygous (Ct) forms of 379V polymorphism were less frequent in MI patients than in controls, suggesting that this allele might be protective against the development of CAd while A379 variant was more prevalent among patients.…”

Relations of Inflammatory Biomarkers and Common Genetic Variants With Arterial Stiffness and Wave Reflection

“…Of note, the 2 top SNPs for Lp-PLA2 activity and RPW are in the PLA2G7 gene and were significantly associated with Lp-PLA2 activity in the Framingham Offspring cohort and in previous studies. 35 In our exploratory analyses, we were not able to show strong evidence for mendelian randomization for the inflammatory biomarkers examined (including Lp-PLA2). We acknowledge that many of the conditions required to infer causality under mendelian randomization were not met in the present project.…”

G/T Substitution in Intron 1 of the UNC13B Gene Is Associated With Increased Risk of Nephropathy in Patients With Type 1 Diabetes

“…For eight additional genes (CCR5, CNDP1, HNF4A, LTA, PON2, GCGR, INPPL1, PLA2G7), polymorphisms were selected according to reported associations with phenotypes relevant for diabetic nephropathy (13)(14)(15)(16)(17)(18)(19)(20). We also examined 94 SNP markers (genomic control markers) in nongenic regions spaced throughout the genome to control for possible stratification within each population (21,22).…”