Plasminogen activator inhibitor 4G polymorphism is associated with decreased risk of cerebrovascular mortality in older women
Plasminogen activator inhibitor 4G polymorphism is associated with decreased risk of cerebrovascular mortality in older women
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DOI：
10.1161/01.cir.101.1.67
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发表时间：
2000-01-04
期刊：
影响因子：
37.8
通讯作者：
Grobbee, DE
中科院分区：
文献类型：
--
作者：
Roest, M;van der Schouw, YT;Grobbee, DE
背景-纤溶酶原激活物抑制剂-1启动子区4G/5G多态性的常见4G等位基因。派-1基因与派-1蛋白的转录增加有关，这可能导致纤溶降低。因此，它已被提出作为一个候选的心肌梗死或stroke.Methods和结果的危险因素，我们研究了派-1 4G/5G基因型和心血管疾病死亡率的风险之间的关系，在一项前瞻性队列研究中，12 239名妇女最初年龄在52和67岁之间，最长随访时间为18年（153 732年随访）。派-1 4G/5G基因型在从尿样品中获得的DNA中测量，尿样品在基线时收集，498名死于心血管疾病的妇女和来自同一队列的512名未死于心血管疾病的妇女的随机样品。派-1 4G/5G基因型与心肌梗死或其他心血管死亡风险无关。然而，与派-1 5G 5G纯合子相比，派-1 4G 4G纯合子的脑血管死亡风险显著降低：相对危险度为0.4，95%CI为0.2 - 0.7，而派-1 4G 5G杂合子与派-1 5G 5G纯合子相比脑血管死亡的相对危险度为0.7，95%CI为0.4 - 1.1。结论-这些发现提示派-1在脑血管病变中的重要作用，可能通过纤溶以外的途径。派-1可以防止动脉粥样硬化斑块的不稳定，或者它可以抑制脑中组织纤溶酶原激活物的神经毒性。
Background-A common 4G allele of a 4G/5G polymorphism in the promoter region of the plasminogen activator inhibitor-1. (PAI-1) gene is associated with increased transcription of the PAI-1 protein, which may lead to decreased fibrinolysis. It has therefore been proposed as a candidate risk factor for myocardial infarction or stroke.Methods and Results-We studied the relationship between PAI-1 4G/5G genotype and the risk of cardiovascular mortality in a prospective cohort study among 12 239 women initially aged between 52 and 67 years, with a maximum follow-up time of 18 years (153 732 follow-up years). PAI-1 4G/5G genotype was measured in DNA obtained from urine samples, which were collected at baseline, of 498 women who died of a cardiovascular disease and a random sample of 512 women from the same cohort who did not die of cardiovascular disease. The PAI-1 4G/5G genotype was not associated with risk of myocardial infarction or other cardiovascular mortality. However, PAI-1 4G4G homozygotes had a markedly reduced risk of cerebrovascular mortality compared with PAI-1 5G5G homozygotes: the relative risk was 0.4, with a 95% CI of 0.2 to 0.7, whereas the relative risk of cerebrovascular mortality in PAI-1 4G5G heterozygotes compared with PAI-1 5G5G homozygotes was 0.7, with a 95% CI of 0.4 to 1.1.Conclusions-These findings are suggestive of an important contribution of PAI-1 in cerebrovascular pathology, probably via pathways other than fibrinolysis. PAI-1 may protect against destabilization of the atherosclerotic plaque, or it may inhibit neurotoxicity of tissue plasminogen activator in the brain.