Nurden A T
URA 1464 CNRS, Hôpital Cardiologique, Pessac, France.
Thromb Haemost. 1995 Jul;74(1):345-51.
The haemostatic response of platelets of any one individual will be influenced by the genetic profile of the total population of receptors expressed on the platelet surface. Among the parameters to consider will be (i) the density of each receptor, (ii) the rate at which genes are transcribed and receptors produced and (iii) the presence or not of structural polymorphisms. Already, consideration of the known polymorphisms on GP IIb and GP IIIa raises most interesting questions on the structure/function relationship for this receptor. For example, there is often no obvious pattern as to which polymorphisms will influence platelet function and which will risk giving rise to a diallelic alloantigen system. Thus, mutation at Arg214 results in a loss in the ability of the complex to support platelet aggregation, whereas a mutation at Arg143 has resulted in the production of an immune response (see above). As I have pointed out earlier, examples from inherited platelet disorders show that even a single mutated allele can influence receptor function. Others have shown that polymorphisms of plasma proteins (see 52) or membrane glycoproteins such as E-selectin of endothelial cells (see 53) can give rise to risk factors for thrombosis and/or atherosclerosis. It would be interesting to know whether polymorphisms of platelet glycoprotein receptors (and those shared with other vascular cells) also represent risk factors in cardiovascular disease.
任何个体血小板的止血反应将受到血小板表面表达的所有受体的基因谱的影响。需要考虑的参数包括：（i）每种受体的密度；（ii）基因转录和受体产生的速率；（iii）结构多态性的存在与否。对已知的糖蛋白IIb和糖蛋白IIIa多态性的研究，已经就该受体的结构/功能关系提出了非常有趣的问题。例如，对于哪些多态性会影响血小板功能以及哪些会产生双等位基因同种异体抗原系统，通常没有明显的模式。因此，精氨酸214处的突变导致复合物支持血小板聚集的能力丧失，而精氨酸143处的突变则引发了免疫反应（见上文）。正如我之前所指出的，遗传性血小板疾病的例子表明，即使是单个突变等位基因也能影响受体功能。其他人已经表明，血浆蛋白（见52）或膜糖蛋白（如内皮细胞的E-选择素，见53）的多态性可导致血栓形成和/或动脉粥样硬化的危险因素。了解血小板糖蛋白受体（以及与其他血管细胞共有的受体）的多态性是否也代表心血管疾病的危险因素将是很有趣的。
