Seguí R, Estellés A, Mira Y, España F, Villa P, Falcó C, Vayá A, Grancha S, Ferrando F, Aznar J
The Research Centre, La Fe University Hospital, Valencia, Spain.
Br J Haematol. 2000 Oct;111(1):122-8. doi: 10.1046/j.1365-2141.2000.02321.x.
Impaired fibrinolysis as a result of increased plasminogen activator inhibitor-1 (PAI-1) levels in plasma is a common finding in patients with deep vein thrombosis (DVT). A 4G/5G polymorphism in the promoter region of the PAI-1 gene has been reported to influence the levels of PAI-1. The 4G allele was found to be associated with higher plasma PAI-1 activity (act), but contradictory results on the incidence of the 4G allele in DVT patients have been reported. The aim of this study was to analyse whether the PAI-1 promoter 4G/5G genotype increases the risk of venous thrombosis in subjects with thrombophilic defects, and to determine the distribution of the PAI-1 4G/5G genotype and its relation to plasma PAI-1 levels in 190 unrelated patients with DVT in comparison with a control group of 152 healthy subjects. No differences between the 4G/5G allele distribution in the DVT group (0.43/0.57) and in the control group (0.42/0.58) were observed. However, the presence of the 4G allele significantly increased the risk of thrombosis in patients with other thrombophilic defects. Significantly higher PAI-1 levels were observed in DVT patients than in the controls. Our results also showed significant differences in the plasma levels of PAI-1 antigen (ag) and PAI-1 act among the 4G/5G genotypes in DVT patients. A multivariate analysis revealed that, in the DVT group, PAI-1 ag levels were influenced by the 4G allele dosage, triglyceride levels and body mass index (BMI). The influence of the 4G allele dosage on PAI-1 levels was independent of the triglyceride levels and BMI. In the control group, no significant correlation between PAI-1 levels and 4G allele dosage was observed. In conclusion, the PAI-1 promoter polymorphism was found to have an influence on PAI-1 levels in DVT patients and on the risk of venous thrombosis in subjects with other genetic thrombophilic defects.
血浆中纤溶酶原激活物抑制剂-1（PAI-1）水平升高导致纤维蛋白溶解受损是深静脉血栓形成（DVT）患者的常见表现。据报道，PAI-1基因启动子区域的4G/5G多态性会影响PAI-1的水平。发现4G等位基因与较高的血浆PAI-1活性（act）相关，但关于DVT患者中4G等位基因发生率的研究结果相互矛盾。本研究的目的是分析PAI-1启动子4G/5G基因型是否会增加具有血栓形成倾向缺陷的受试者发生静脉血栓形成的风险，并确定190例无亲缘关系的DVT患者与152例健康对照者中PAI-1 4G/5G基因型的分布及其与血浆PAI-1水平的关系。未观察到DVT组（0.43/0.57）和对照组（0.42/0.58）之间4G/5G等位基因分布的差异。然而，4G等位基因的存在显著增加了具有其他血栓形成倾向缺陷患者的血栓形成风险。观察到DVT患者的PAI-1水平显著高于对照组。我们的结果还显示，DVT患者中4G/5G基因型之间的PAI-1抗原（ag）和PAI-1 act血浆水平存在显著差异。多变量分析显示，在DVT组中，PAI-1 ag水平受4G等位基因剂量、甘油三酯水平和体重指数（BMI）的影响。4G等位基因剂量对PAI-1水平的影响独立于甘油三酯水平和BMI。在对照组中，未观察到PAI-1水平与4G等位基因剂量之间的显著相关性。总之，发现PAI-1启动子多态性对DVT患者的PAI-1水平以及具有其他遗传性血栓形成倾向缺陷的受试者的静脉血栓形成风险有影响。
