BACKGROUND: Oxidation of low density lipoproteins is an initial step of atherogenesis that generates pro-inflammatory phospholipids, including platelet-activating factor (PAF). PAF is degraded by PAF-acetylhydrolase (PAF-AH), which has been postulated to be a risk factor for myocardial infarction (MI). The role of PAF-AH for the onset of premature MI is unclear. METHODS: Polymorphisms located in putatively functional regions were investigated in a cohort of patients having premature MI onset prior to 46 years of age (n = 200) and a sex-age-matched control group (n = 200). The activity of PAF-AH and coronary angiograms were evaluated for the severity of coronary atherosclerosis. RESULTS: The V allele of A379V (exon 11) polymorphism on PAF-AH gene was more frequent in patients with premature MI (P = 0.001). This V allele polymorphism was also associated with a lower activity of plasma PAF-AH and a more complex coronary atherosclerosis (p Trends <0.05). Multiple logistic regression analysis showed that this polymorphism was an independent risk factor (Odds Ratio [OR] 1.66, 95% CI 1.14.1 to 5.80, P = 0.008) as well as smoking (OR 3.72, 95% CI 1.77 to 9.28, P = 0.001), diabetes mellitus (OR 2.25, 95% CI 1.40 to 5.32, P = 0.007) and hypertension (OR 1.88, 95% CI 1.25 to 5.36, P = 0.003) for the onset of premature MI. CONCLUSION: We conclude that a functional and significant association between the A379V polymorphism on exon 11 of PAF-AH gene and premature MI exists in this Taiwanese population. This polymorphism is significantly associated with the PAF-AH activity and the severity of coronary atherosclerosis.
BACKGROUND: Oxidation of low density lipoproteins is an initial step of atherogenesis that generates pro-inflammatory phospholipids, including platelet-activating factor (PAF). PAF is degraded by PAF-acetylhydrolase (PAF-AH), which has been postulated to be a risk factor for myocardial infarction (MI). The role of PAF-AH for the onset of premature MI is unclear. METHODS: Polymorphisms located in putatively functional regions were investigated in a cohort of patients having premature MI onset prior to 46 years of age (n = 200) and a sex-age-matched control group (n = 200). The activity of PAF-AH and coronary angiograms were evaluated for the severity of coronary atherosclerosis. RESULTS: The V allele of A379V (exon 11) polymorphism on PAF-AH gene was more frequent in patients with premature MI (P = 0.001). This V allele polymorphism was also associated with a lower activity of plasma PAF-AH and a more complex coronary atherosclerosis (p Trends <0.05). Multiple logistic regression analysis showed that this polymorphism was an independent risk factor (Odds Ratio [OR] 1.66, 95% CI 1.14.1 to 5.80, P = 0.008) as well as smoking (OR 3.72, 95% CI 1.77 to 9.28, P = 0.001), diabetes mellitus (OR 2.25, 95% CI 1.40 to 5.32, P = 0.007) and hypertension (OR 1.88, 95% CI 1.25 to 5.36, P = 0.003) for the onset of premature MI. CONCLUSION: We conclude that a functional and significant association between the A379V polymorphism on exon 11 of PAF-AH gene and premature MI exists in this Taiwanese population. This polymorphism is significantly associated with the PAF-AH activity and the severity of coronary atherosclerosis.
Authors: Beth S Sutton; David R Crosslin; Svati H Shah; Sarah C Nelson; Anthony Bassil; A Brent Hale; Carol Haynes; Pascal J Goldschmidt-Clermont; Jeffery M Vance; David Seo; William E Kraus; Simon G Gregory; Elizabeth R Hauser Journal: Hum Mol Genet Date: 2008-01-18 Impact factor: 6.150
Authors: Sunil Suchindran; David Rivedal; John R Guyton; Tom Milledge; Xiaoyi Gao; Ashlee Benjamin; Jennifer Rowell; Geoffrey S Ginsburg; Jeanette J McCarthy Journal: PLoS Genet Date: 2010-04-29 Impact factor: 5.917
Authors: Renate Schnabel; Josée Dupuis; Martin G Larson; Kathryn L Lunetta; Sander J Robins; Yanyan Zhu; Jian Rong; Xiaoyan Yin; Heide A Stirnadel; Jeanne J Nelson; Peter W F Wilson; John F Keaney; Ramachandran S Vasan; Emelia J Benjamin Journal: Atherosclerosis Date: 2008-11-05 Impact factor: 5.162