Polymorphisms of human platelet membrane glycoproteins: structure and clinical significance.
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.
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URA 1464 CNRS, Hôpital Cardiologique, Pessac, France.
D000595:Amino Acid Sequence; D016824:Antigens, Human Platelet / Q000235:genetics; D001791:Blood Platelet Disorders / Q000235:genetics; D006801:Humans; D016023:Integrins / Q000235:genetics; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010974:Platelet Aggregation; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D010980:Platelet Membrane Glycoproteins / Q000737:chemistry / Q000172:deficiency / Q000235:genetics* / Q000502:physiology; D011110:Polymorphism, Genetic; D038981:Receptors, Collagen; D019030:Receptors, Vitronectin / Q000502:physiology
D016824:Antigens, Human Platelet; D016023:Integrins; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D019038:Platelet Glycoprotein GPIb-IX Complex; D010980:Platelet Membrane Glycoproteins; D038981:Receptors, Collagen; D019030:Receptors, Vitronectin