The 4G/5G polymorphism in the plasminogen activator inhibitor-1 gene is not associated with myocardial infarction
The 4G/5G polymorphism in the plasminogen activator inhibitor-1 gene is not associated with myocardial infarction
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DOI：
10.1055/s-0037-1614639
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发表时间：
1999-07-01
影响因子：
6.7
通讯作者：
Rosendaal, FR
中科院分区：
文献类型：
--
作者：
Doggen, CJM;Bertina, RM;Rosendaal, FR
多项研究发现高纤溶酶原激活剂抑制剂-1 (PAI-1) 水平与心肌梗塞之间存在关联。目前尚不清楚这是否是动脉粥样硬化或组织损伤的因果关系或结果。在一些研究中，但并非全部，与健康人中 5G 等位基因携带者相比，PAI-1 基因中 4G/5G 多态性的 4G 等位基因纯合携带者具有更高的 PAI-1 水平。如果 PAI-1 水平与心肌梗死存在因果关系，则可以预期患者中会有更多的 4G 等位基因纯合携带者，前提是这些携带者在该人群的健康人中具有较高的 PAI-1 水平。我们在“莱顿心肌梗塞研究”(SMILE) 中调查了这种多态性的分布，包括 331 名患有心肌梗塞的男性和 302 名对照受试者，并测量了后者的 PAI-1 抗原水平。其次，我们研究了心血管危险因素与PAI-1水平的关系。我们没有发现4G等位基因携带者心肌梗死的风险增加。我们没有发现对照受试者的 4G/5G 多态性与 PAI-1 抗原水平之间存在关联或趋势。与没有这些因素的人相比，患有肥胖、高血压或吸烟的对照者的 PAI-1 抗原水平显着升高。高胆固醇和甘油三酯水平也与高PAI-1抗原水平相关，HDL-胆固醇水平呈负相关。我们得出结论，PAI-1基因中的4G/5G多态性与心肌梗死的风险无关。由于我们没有发现健康人中这种多态性与 PAI-1 抗原水平之间存在任何关联，因此我们无法就 PAI-1 本身与心肌梗死的因果关系得出任何结论。
Several studies have found an association between high plasminogen activator inhibitor-1 (PAI-1) levels and myocardial infarction. Whether this is causal or a consequence of atherosclerosis or tissue damage, remains unclear. Homozygous carriers of the 4G allele of the 4G/5G polymorphism in the PAI-1 gene have higher PAI-1 levels compared to carriers of the 5G allele in healthy persons in some studies, but not all. If PAI-1 levels are causally related to myocardial infarction, one would expect more homozygous carriers of the 4G allele among patients, provided that these carriers have high PAI-1 levels among healthy persons in that population. We investigated the distribution of this polymorphism in the "Study of Myocardial Infarctions Leiden" (SMILE), including 331 men with a myocardial infarction and 302 control subjects and measured PAI-1 antigen levels among the latter. Secondly, we looked into the association of cardiovascular risk factors with PAI-1 levels.We did not find an increase in risk of myocardial infarction in carriers of the 4G allele. Neither did we find an association, nor a trend, between the 4G/5G polymorphism and PAI-1 antigen levels in control subjects. Controls with obesity, hypertension, or who smoked had significant higher PAI-1 antigen levels compared with persons without these factors. High cholesterol and triglyceride levels were also associated with high PAI-1 antigen levels, and HDL-cholesterol levels showed an inverse association.We conclude that the 4G/5G polymorphism in the PAI-1 gene is not associated with the risk of myocardial infarction. As we did not find any association between this polymorphism and PAI-1 antigen levels in healthy persons, we cannot draw any conclusions about the causality of PAI-1 itself for myocardial infarction.