Platelet-activating factor-acetylhydrolase (PLA2G7) A379V (exon 11) gene polymorphism is functionally associated with coronary artery disease severity but not the onset of acute coronary syndrome

Background: Oxidation of low-density lipoproteins is an initial step of atherogenesis that generates proinflammatory phospholipids, including platelet-activating factor (PAF). PAF is degraded by PAF-acetylhydrolase (PAF-AH), which is also a risk factor for myocardial infarction. The role of PAF-AH in the onset of acute coronary syndrome (ACS) and its association with atherosclerosis among ACS patients are still unclear. Methods: PAF-AH encoding gene (PLA2G7) A379V variation was investigated in a cohort of patients having ACS (n = 200) and a sex-age-matched control group (n = 200). The activity of PAF-AH was evaluated by ELISA assay and coronary angiograms were evaluated among 100 ACS subjects for the severity of coronary atherosclerosis. Results: The V allele of A379V (exon 11) polymorphism on the PLA2G7 gene was more frequent in ACS patients (p = 0.02). This V allele polymorphism was also associated with a lower activity of plasma PAF-AH (VV vs. VA vs. AA: 9.8 ± 5.3 vs. 20.5 ± 7.7 vs. 24.8 ± 5.9 nmol/mL, respectively;p for trend = 0.03) and a more complex coronary atherosclerosis (diffuse score: VV vs. VA vs. AA: 7.3 ± 1.7 vs. 5.2 ± 1.4 vs. 3.4 ± 1.3, respectively;p for trend = 0.04). Multiple logistic regression analysis revealed three independent risk factors: smoking (OR 2.14, 95% CI 1.77 to 8.10, p = 0.02), diabetes mellitus (OR 2.08, 95% CI 1.55 to 5.32, p = 0.007) and hypertension (OR 3.18, 95% CI 1.15 to 7.36, p = 0.002), were all independent risk factors for the onset of ACS. However, this genetic variation did not show significant difference (OR 1.21, 95% CI 0.89 to 5.80, p = 0.18). Conclusion: We conclude that the PLA2G7/A379V polymorphism on exon 11 of PAF-AH gene is functionally associated with the PAF-AH activity and the severity of coronary atherosclerosis, but not onset of ACS, among Taiwanese population.