Akar N, Yilmaz E, Akar E, Avcu F, Yalçin A, Cin S
Ankara University Department of Pediatric Molecular Genetics, Turkey.
Thromb Res. 2000 Feb 15;97(4):227-30. doi: 10.1016/s0049-3848(99)00164-4.
A decreased fibrinolytic activity due to increased levels of plasminogen activator inhibitor-1 has been shown in deep vein thrombosis patients. Elevated plasma plasminogen activator inhibitor-1 levels are associated with the 4G allele of a 4G/5G polymorphism located in the promoter region of the plasminogen activator inhibitor-1 gene. Because there is no existing data in the Turkish population, we aimed to study these mutations in patients with deep vein thrombosis (n = 136) and normal controls (n = 113), consecutively selected among unrelated healthy subjects without personal and familial history of atherothrombosis from Ankara, Turkey. DNA was extracted by conventional methods, and polymerase chain reaction of the plasminogen activator inhibitor-1 4G/5G polymorphism was performed according to a previously described method. Genotype distributions of FV 1691G-A and plasminogen activator inhibitor-1 4G/5G are as follows: plasminogen activator inhibitor-1 4G (patients) 0.562, plasminogen activator inhibitor-1 4G (controls) 0.50 (p = 0.6); FV1691A (patients) 0.147, FV1691A (controls) 0.035 (p = 0.005). Our data indicated that plasminogen activator inhibitor-1 4G/5G does not have an effect on the thrombotic risk. Carrying the 4G allele either in heterozygous or homozygous state increases the risk in the presence of FV1691A (odds ratio: 9.8 and 6.9, confidence interval 95% 2.9-32.7 and 1.3-35.8). FV1691A is an independent risk factor for thrombosis (odds ratio: 5.5, confidence interval: 95% 2.5-12.1). We concluded that coexistence of FV1691A and plasminogen activator inhibitor-1 4G allele leads to an increased risk for thrombosis leading a further evidence to another prothrombotic factor that may be necessary for the development of a manifest thrombotic event.
深静脉血栓形成患者中已显示出由于纤溶酶原激活物抑制剂-1水平升高导致纤溶活性降低。血浆纤溶酶原激活物抑制剂-1水平升高与位于纤溶酶原激活物抑制剂-1基因启动子区域的4G/5G多态性的4G等位基因相关。由于土耳其人群中尚无现有数据，我们旨在研究来自土耳其安卡拉的深静脉血栓形成患者（n = 136）和正常对照（n = 113）中的这些突变，这些对照是从无动脉粥样硬化血栓形成个人和家族史的无关健康受试者中连续选取的。通过常规方法提取DNA，并根据先前描述的方法对纤溶酶原激活物抑制剂-1的4G/5G多态性进行聚合酶链反应。FV 1691G-A和纤溶酶原激活物抑制剂-1 4G/5G的基因型分布如下：纤溶酶原激活物抑制剂-１ 4G（患者）0.562，纤溶酶原激活物抑制剂-1 4G（对照）0.50（p = 0.6）；FV1691A（患者）0.147，FV1691A（对照）0.035（p = 0.005）。我们的数据表明，纤溶酶原激活物抑制剂-1 4G/5G对血栓形成风险没有影响。杂合或纯合状态携带4G等位基因在存在FV1691A时会增加风险（优势比：9.8和6.9，95％置信区间2.9-32.7和1.3-35.8）。FV1691A是血栓形成的独立危险因素（优势比：5.5，置信区间：95％ 2.5-12.1）。我们得出结论，FV1691A和纤溶酶原激活物抑制剂-1 4G等位基因共存会导致血栓形成风险增加，这为明显血栓形成事件发生可能必需的另一种促血栓形成因素提供了进一步的证据。
