Role of hemostatic gene polymorphisms in venous and arterial thrombotic disease

作     者：Lane, DA Grant, PJ 

作者机构：Univ London Imperial Coll Sci Technol & Med Sch Med Dept Hematol London W6 8RP England Univ Leeds Acad Unit Mol Vasc Med Leeds W Yorkshire England 

出 版 物：《BLOOD》 (Blood)

年 卷 期：2000年第95卷第5期

页      面：1517-1532页

核心收录：

学科分类：1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 10[医学] 

主　　题：3'非翻译区 动脉闭塞性疾病/流行病学 动脉闭塞性疾病/遗传学 血液凝固因子/遗传学 因子Ⅴ/遗传学 因子Ⅶ/遗传学 因子ⅩⅢ/遗传学 纤维蛋白原/遗传学 纤维蛋白溶解/遗传学 疾病遗传易感性 止血/遗传学 高同种半胱氨酸血症/流行病学 高同种半胱氨酸血症/遗传学 纤溶酶原激活物抑制物1/遗传学 血小板膜糖蛋白类/遗传学 点突变 多态现象 遗传 凝血酶原/遗传学 受体 细胞表面/遗传学 危险因素 序列缺失 血栓栓塞/流行病学 血栓栓塞/遗传学 血栓形成倾向/流行病学 血栓形成倾向/遗传学 组织型纤溶酶原激活物/遗传学 静脉血栓形成/流行病学 静脉血栓形成/遗传学 人类 

摘      要：A casual glance at a rapidly expanding literature could easily lead to the conclusion that we are well on the way to establishing the genetic basis for vascular disorders, such is the number of polymorphisms that have been investigated (see summary Table 1). There has clearly been appreciable progress in relation to venous thromboembolic disease whereby the functional and clinical conse- quences of certain polymorphisms are accepted. Venous disease occurs in the context of a low-pressure, low-ow system in which atheroma does not occur. The most common genetic risk determi- nant for venous disease alters the function of the protein C anticoagulant pathway, whereas other genetic risk factors alter levels or activities of certain coagulation *** environ- mental inuences are undoubtedly important, genetic changes can play a crucial role and even sometimes lead to apparently spontaneous venous disease. In contrast, there is little clarity in relation to arterial disease (see Table 1). The initial promise that genetic risk factors might contribute appreciably to an explanation of the development of arterial disease has largely been unfullled, and the expectations raised by early reports of positive associations have been tempered by inconsistent results with almost all genes studied. Arterial disease occurs in a high-pressure, high-ow system with atheroma- tous disease as a dominant feature. Hemostatic factors have been extensively studied as possible risk determinants for disease. The most consistent associations have been found for brinogen. Although it is formally possible that brinogen is merely a marker of another underlying process, such as the acute-phase reaction,226 a strong case can be made that brinogen is causally involved in disease. For each of the other hemostatic factors, though a causal role is highly plausible, the evidence for this is less strong. It is interesting to note that hemostatic risk factors for atherothrombotic disorders are larg