Goodall A H, Curzen N, Panesar M, Hurd C, Knight C J, Ouwehand W H, Fox K M
Division of Chemical Pathology, University of Leicester, Glenfield Hospital, UK.
Eur Heart J. 1999 May;20(10):742-7. doi: 10.1053/euhj.1998.1203.
The GPIIb-IIIa complex on the platelet membrane plays an important part in thrombosis as it is the receptor for fibrinogen. The gene for platelet membrane glyco-protein IIIa has multiple alleles one of which, the GPIIIa-Proline33 (HPA-1b, PlA2, Zwb) allele has been reported in some, but not all studies, to be associated with an increased risk of myocardial infarction. We investigated whether the presence of the Pro33 form of GPIIIa on the platelet membrane is associated with increased fibrinogen binding.
Blood samples from 70 patients (54 male) with stable angina of whom 22 (18 male) had a history of previous myocardial infarction, were analysed for the GPIIIa-Leu-Pro33 polymorphism at the genomic level, and for whole blood flow cytometric measurement of platelet fibrinogen binding. The GPIIIa-Pro33 form was present in 20 (28.6%) patients (1 homozygous) representing an allele frequency of 0.85 and 0.15 (GPIIIa-Leu33:Pro33). The incidence of myocardial infarction was higher (40.0%) in patients positive for GPIIIa-Pro33 than in those without (32.0%) but this was not significant (P=0.58). Fibrinogen binding to ADP-stimulated platelets was significantly higher in the GPIIIa-Pro33 positive group at all ADP concentrations (<0.0001; two way ANOVA). There was no association between fibrinogen binding and the level of expression of the GPIIb-IIIa complex, platelet volume or platelet count. Fibrinogen binding in response to thrombin stimulation was not different between the groups (P>0.05).
The increased tendency of platelets from patients with the Pro33 form of GPIIIa may predispose patients with this allele to a higher risk of acute thrombotic events, and argues for selective use of therapeutic agents that inhibit ADP-mediated platelet activation in occlusive vascular disease states.
血小板膜上的糖蛋白IIb-IIIa复合物作为纤维蛋白原的受体，在血栓形成过程中发挥重要作用。血小板膜糖蛋白IIIa基因具有多个等位基因，其中之一，即糖蛋白IIIa-脯氨酸33（HPA-1b、PlA2、Zwb）等位基因，在部分（而非全部）研究中被报道与心肌梗死风险增加相关。我们研究了血小板膜上糖蛋白IIIa的脯氨酸33形式的存在是否与纤维蛋白原结合增加有关。
对70例（54例男性）稳定型心绞痛患者的血样进行分析，其中22例（18例男性）有既往心肌梗死病史，在基因组水平分析糖蛋白IIIa-亮氨酸-脯氨酸33多态性，并通过全血流式细胞术检测血小板纤维蛋白原结合情况。糖蛋白IIIa-脯氨酸33形式存在于20例（28.6%）患者中（1例纯合子），等位基因频率分别为0.85和0.15（糖蛋白IIIa-亮氨酸33：脯氨酸33）。糖蛋白IIIa-脯氨酸33阳性患者的心肌梗死发生率（40.0%）高于阴性患者（32.0%），但差异无统计学意义（P = 0.58）。在所有ADP浓度下，糖蛋白IIIa-脯氨酸33阳性组中，纤维蛋白原与ADP刺激的血小板的结合均显著更高（<0.0001；双向方差分析）。纤维蛋白原结合与糖蛋白IIb-IIIa复合物的表达水平、血小板体积或血小板计数之间无关联。两组之间凝血酶刺激后的纤维蛋白原结合无差异（P>0.05）。
具有脯氨酸33形式糖蛋白IIIa的患者的血小板增加的倾向性可能使携带该等位基因的患者发生急性血栓事件的风险更高，这支持在闭塞性血管疾病状态下选择性使用抑制ADP介导的血小板活化的治疗药物。
