Department of Medicine, Division of Research, New England Baptist Hospital, Harvard Medical School, Boston, MA, USA.
Clin Appl Thromb Hemost. 2010 Oct;16(5):574-8. doi: 10.1177/1076029610361334.
Plasminogen activator Inhibitor 1 (PAI-1) inhibits plasminogen activators leading to decreased fibrinolysis and increased risk of thromboembolic disease (TED). Shifts in PAI-1 promoter genome from normal 5G>5G to 4G>5G or 4G>4G alleles are associated with overexpression of PAI-1. In this study patients with residual venous thrombi were observed to have increased PAI-1 levels and more frequent shifts to 4G alleles. Of the 26, 20 (76.9%) patients with unresolved thrombus had elevated PAI-1 values. 4G genomic shifts were found in 92.9% patients studied. Normal PAI-1 levels were found in 5 patients with 4G polymorphisms. Thus, PAI-1 is often elevated among patients with residual thrombus, with an unexpectedly high prevalence of the 4G polymorphism of the promoter genome. Patients with persistent thrombus should be considered at risk of having constituently increased PAI-1 due to genomic changes in the PAI-1 promoter genome. Hypotheses are proposed to explain those with normal PAI-1, despite having 4G polymorphisms.
纤溶酶原激活物抑制剂 1（PAI-1）抑制纤溶酶原激活物，导致纤维蛋白溶解减少和血栓栓塞性疾病（TED）风险增加。PAI-1 启动子基因组从正常的 5G>5G 转变为 4G>5G 或 4G>4G 等位基因与 PAI-1 的过度表达有关。在这项研究中，观察到残留静脉血栓的患者 PAI-1 水平升高，并且更频繁地发生 4G 等位基因转变。在未解决血栓的 26 名患者中，有 20 名（76.9%）患者的 PAI-1 值升高。在研究的 92.9%的患者中发现了 4G 基因组转变。在 5 名具有 4G 多态性的患者中发现了正常的 PAI-1 水平。因此，残留血栓患者的 PAI-1 水平通常升高，启动子基因组的 4G 多态性发生率出乎意料地高。持续存在血栓的患者应被认为存在 PAI-1 持续增加的风险，这是由于 PAI-1 启动子基因组的基因变化所致。提出了一些假设来解释那些尽管存在 4G 多态性但 PAI-1 水平正常的患者。
