Plasminogen Activator Inhibitor-1 (PAI-1) 4G/5G Promoter Polymorphism and Levels in Subjects with Cerebrovascular Disease
Plasminogen Activator Inhibitor-1 (PAI-1) 4G/5G Promoter Polymorphism and Levels in Subjects with Cerebrovascular Disease
复制标题
脑血管疾病受试者中纤溶酶原激活剂抑制剂 1 (PAI-1) 4G/5G 启动子多态性和水平
作者：
A. Catto;A. Carter;M. Stickland;J. Bamford;J. Davies;P. Grant
纤溶系统在卒中发病机制中的确切作用尚待确定。血纤溶酶原激活物抑制剂-1（纤溶系统的主要灭活剂）循环水平升高与心肌梗死的发生有关。有证据表明派-1基因启动子区的多态性与循环派-1水平相关。我们研究了一个共同的单核苷酸插入/缺失（4G/5G）多态性的PCR在558例脑卒中患者，其中的病理类型是由颅脑计算机断层扫描，并在172名对照。研究4G/5G基因型和派-1活性与1）卒中类型和2）卒中后4周、3个月和6个月内发生的死亡率的关系。将所有中风病例与对照组进行比较，也未观察到临床确定的脑梗死亚型之间的基因型频率差异。在配对样本中，卒中患者（n = 245）在发病时（11.6 U/ml）和3个月后（11.8 U/ml）的派-1活性均显著高于对照组（8.8 U/ml，p <0.0001）。分别有37例（6.2%）、86例（14.5%）和122例（20.5%）患者在入院后1、3和6个月内死亡。派-1活性与卒中后1个月和3个月的全因死亡率独立相关（分别为p = 0.02和p = 0.03），但在6个月后不相关。在该人群中，4G/5G启动子多态性与卒中风险增加无关。派-1水平在急性中风时升高，并在三个月后持续存在。派-1水平而非基因型与卒中后早期死亡率相关。
Summary The exact role of the fibrinolytic system in the pathogenesis of stroke remains to be established. Elevated circulating levels of plasminogen activator inhibitor-1, the principle inactivator of the fibrinolytic system, have been related to the development of myocardial infarction. There is evidence that a polymorphism in the promoter region of the PAI-1 gene is associated with circulating PAI-1 levels. We studied a common single nucleotide insertion/deletion (4G/5G) polymorphism by PCR in 558 patients with stroke, the pathological type of which was established by cranial computed tomography, and in 172 controls. 4G/5G genotype and PAI-1 activity were investigated in relation to 1) stroke type and 2) mortality occurring within four weeks, three months and six months of the stroke. No difference in genotype frequency was observed when all cases of stroke were compared with controls nor between the clinically determined subtypes of cerebral infarction. PAI-1 activity was significantly higher in patients with stroke (n = 245) both at presentation (11.6 U/ml) and after three months (11.8 U/ml), in paired samples, than in control subjects (8.8 U/ml, p <0.0001). Thirty-seven (6.2%), 86 (14.5%) and 122 (20.5%) patients had died within one, three and six months of admission, respectively. PAI-1 activity was independently associated with all-cause mortality at one and three months after stroke (p = 0.02 and p = 0.03 respectively), but not after six months. In this population the 4G/5G promoter polymorphism is not associated with an increased risk of stroke. PAI-1 levels were elevated at the time of acute stroke which persisted after three months. PAI-1 level but not genotype was associated with early mortality following stroke.
DOI：
10.1073/pnas.89.15.6998
发表时间：
1992-08-01
影响因子：
11.1
作者：
SCHNEIDERMAN, J;SAWDEY, MS;LOSKUTOFF, DJ
通讯作者：
LOSKUTOFF, DJ