Murata M, Kawano K, Matsubara Y, Ishikawa K, Watanabe K, Ikeda Y
Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.
Semin Thromb Hemost. 1998;24(3):245-50. doi: 10.1055/s-2007-995849.
The fact that certain ethnic groups and specific populations residing in certain geographic areas carry an increased risk for thrombosis and that thrombosis occurs in young patients without established risk factors indicates the presence of new, previously unrecognized inherited conditions predisposing to thrombosis. We are now aware that interindividual variations within the loci coding for proteins relevant to lipid and vascular metabolisms as well as blood coagulation are universally found. Platelets play central roles in cerebrovascular diseases and acute coronary syndromes, as demonstrated by histopathological findings and clinical observations showing the efficacy of antiplatelet therapies for these disorders. In this article, we show our recent findings on the association between coronary artery disease (CAD) and polymorphisms in platelet membrane glycoproteins. The glycoprotein (GP) Ib/IX complex is a receptor for von Willebrand factor, which mediates shear stress-dependent platelet activation. It has recently been implicated in the pathogenesis of acute coronary syndromes. We have determined genotypes of the "size-polymorphism" of GPIb alpha--i.e., the variable number (1-4) of a 13 amino acid sequence (399-411)--in angiographically proven Japanese CAD patients with myocardial infarction or angina pectoris as well as in individuals from the general population with no history of angina or other heart diseases and normal resting electrocardiograms (ECG). We have found that the genotypes having at least one 4-repeat allele (4R) are more frequently found in patients than in controls. Logistic regression analyses for the adjustment of age, sex, and other acquired coronary risk factors provided an odds ratio of 7.94 (p=0.0043) for those with 4R vs. those without 4R, suggesting that the presence of 4R is an independent risk factor for CAD. The molecular mechanisms underlying this association are currently under investigation. Relationships between arterial thrombosis and polymorphisms in other platelet GPs (collagen receptor and fibrinogen receptor), blood coagulation factors, fibrinolytic factors, vasoactive substances, and factors relevant for lipid metabolisms are also discussed.
某些种族群体以及居住在特定地理区域的特定人群发生血栓形成的风险增加，而且在没有既定风险因素的年轻患者中也会发生血栓形成，这表明存在新的、以前未被认识的易导致血栓形成的遗传性疾病。我们现在知道，在编码与脂质和血管代谢以及血液凝固相关蛋白质的基因座内普遍存在个体差异。组织病理学发现和临床观察表明抗血小板疗法对这些疾病有效，这证明血小板在脑血管疾病和急性冠状动脉综合征中起核心作用。在本文中，我们展示了我们最近关于冠状动脉疾病（CAD）与血小板膜糖蛋白多态性之间关联的研究结果。糖蛋白（GP）Ib/IX复合物是血管性血友病因子的受体，它介导剪切应力依赖性血小板活化。最近它被认为与急性冠状动脉综合征的发病机制有关。我们已经确定了经血管造影证实患有心肌梗死或心绞痛的日本CAD患者以及来自普通人群且无心绞痛或其他心脏病史且静息心电图（ECG）正常的个体中GPIbα“大小多态性”的基因型，即13个氨基酸序列（399 - 411）的可变数量（1 - 4）。我们发现，至少有一个4重复等位基因（4R）的基因型在患者中比对照组中更常见。对年龄、性别和其他获得性冠状动脉危险因素进行调整的逻辑回归分析显示，4R携带者与非4R携带者相比的优势比为7.94（p = 0.0043），这表明4R的存在是CAD的独立危险因素。这种关联背后潜在的分子机制目前正在研究中。还讨论了动脉血栓形成与其他血小板糖蛋白（胶原受体和纤维蛋白原受体）、凝血因子、纤溶因子、血管活性物质以及脂质代谢相关因子多态性之间的关系。
