Doggen C J, Bertina R M, Cats V M, Reitsma P H, Rosendaal F R
Department of Clinical Epidemiology, Leiden University Medical Center, The Netherlands.
Thromb Haemost. 1999 Jul;82(1):115-20.
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.
多项研究发现，高纤溶酶原激活物抑制剂-1（PAI-1）水平与心肌梗死之间存在关联。这是因果关系，还是动脉粥样硬化或组织损伤的结果，仍不清楚。在一些研究中，PAI-1基因4G/5G多态性的4G等位基因纯合携带者与健康人群中5G等位基因携带者相比，PAI-1水平更高，但并非所有研究均如此。如果PAI-1水平与心肌梗死存在因果关系，那么在患者中4G等位基因的纯合携带者应该更多，前提是这些携带者在该人群的健康个体中PAI-1水平较高。我们在“莱顿心肌梗死研究”（SMILE）中调查了这种多态性的分布情况，该研究包括331名心肌梗死男性患者和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水平之间的关联。我们未发现4G等位基因携带者发生心肌梗死的风险增加。在对照受试者中，我们也未发现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，患有肥胖症、高血压或吸烟的对照者的PAI-1抗原水平显著更高。高胆固醇和甘油三酯水平也与高PAI-1抗原水平相关，而高密度脂蛋白胆固醇水平呈负相关。我们得出结论，PAI-1基因的4G/5G多态性与心肌梗死风险无关。由于我们未发现这种多态性与健康个体的PAI-1抗原水平之间存在任何关联，因此我们无法就PAI-1本身对心肌梗死的因果关系得出任何结论。
