Cadroy Y, Sakariassen K S, Charlet J P, Thalamas C, Boneu B, Sie P
Laboratoire de Recherche sur l'Hémostase et la Thrombose, Pavillon Lefèbvre, and Centre d'Investigation Clinique, CHU Purpan, Toulouse Cedex, France.
Blood. 2001 Nov 15;98(10):3159-61. doi: 10.1182/blood.v98.10.3159.
This study investigates whether the polymorphisms of 3 important platelet receptors affected experimental thrombus formation in men. Forty healthy male volunteers randomly recruited were genotyped for the variable number of tandem repeat (VNTR) of GPIbalpha, the -5T/C polymorphism in the Kozak sequence of GPIbalpha, the 807C/T polymorphism of GPIa, and the PI(A1)/PI(A2) polymorphism of GPIIb/IIIa. Platelet thrombus formation was induced ex vivo by exposing a collagen-coated coverslip in a parallel plate perfusion chamber to native blood for 4 minutes. The shear rates at the collagen surface were 650 and 2600 x s(-1). At 2600 x s(-1) platelet thrombus formation was significantly related only to the 807C/T polymorphism. In contrast, at 650 x s(-1) thrombus formation was significantly altered only by the Kozak sequence polymorphism. The VNTR and the PI(A1)/PI(A2) polymorphisms did not influence thrombus formation. Thus, platelet thrombus formation is significantly influenced by genetic variations of the GPIbalpha and GPIa receptors. The effect of these polymorphisms was dependent on the blood flow rate.
本研究调查了3种重要血小板受体的多态性是否会影响男性的实验性血栓形成。随机招募了40名健康男性志愿者,对其进行糖蛋白Ibα(GPIbalpha)串联重复序列可变数目(VNTR)、GPIbalpha Kozak序列中的-5T/C多态性、糖蛋白Ia(GPIa)的807C/T多态性以及糖蛋白IIb/IIIa的PI(A1)/PI(A2)多态性的基因分型。通过在平行板灌注室中将胶原包被的盖玻片暴露于全血4分钟,体外诱导血小板血栓形成。胶原表面的剪切速率为650和2600×秒-1。在2600×秒-1时,血小板血栓形成仅与807C/T多态性显著相关。相反,在650×秒-1时,血栓形成仅因Kozak序列多态性而发生显著改变。VNTR和PI(A1)/PI(A2)多态性不影响血栓形成。因此,血小板血栓形成受GPIbalpha和GPIa受体基因变异的显著影响。这些多态性的作用取决于血流速度。