Liu P-Y, Li Y-H, Wu H-L, Chao T-H, Tsai L-M, Lin L-J, Shi G-Y, Chen J-H
Division of Cardiology, Departments of Internal Medicine, National Cheng-Kung University Medical Center, 138 Sheng-Li Road, Tainan 704, Taiwan.
J Thromb Haemost. 2006 May;4(5):1023-8. doi: 10.1111/j.1538-7836.2006.01895.x.
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.
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.
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.
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.
低密度脂蛋白氧化是动脉粥样硬化形成的起始步骤，会产生促炎磷脂，包括血小板活化因子（PAF）。PAF由PAF - 乙酰水解酶（PAF - AH）降解，PAF - AH被认为是心肌梗死（MI）的一个风险因素。PAF - AH在早发性MI发病中的作用尚不清楚。
在一组46岁之前发生早发性MI的患者（n = 200）和一个性别年龄匹配的对照组（n = 200）中，研究位于假定功能区域的多态性。评估PAF - AH活性和冠状动脉造影以确定冠状动脉粥样硬化的严重程度。
PAF - AH基因A379V（外显子11）多态性的V等位基因在早发性MI患者中更常见（P = 0.001）。这种V等位基因多态性还与血浆PAF - AH活性降低和更复杂的冠状动脉粥样硬化相关（p趋势<0.05）。多因素逻辑回归分析表明，这种多态性是早发性MI发病的独立危险因素（优势比[OR] 1.66，95%可信区间1.14至5.80，P = 0.008），吸烟（OR 3.72，95%可信区间1.77至9.28，P = 0.001）、糖尿病（OR 2.25，95%可信区间1.40至5.32，P = 0.007）和高血压（OR 1.88，95%可信区间1.25至5.36，P = 0.003）也是早发性MI发病的危险因素。
我们得出结论，在这个台湾人群中，PAF - AH基因外显子11的A379V多态性与早发性MI之间存在功能上的显著关联。这种多态性与PAF - AH活性和冠状动脉粥样硬化的严重程度显著相关。
