Increased binding of fibrinogen to glycoprotein IIIa-Proline33 (HPA-1b, PlA2, Zwb) positive platelets in patients with cardiovascular disease
Increased binding of fibrinogen to glycoprotein IIIa-Proline33 (HPA-1b, PlA2, Zwb) positive platelets in patients with cardiovascular disease
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DOI：
10.1053/euhj.1998.1203
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发表时间：
1999-05-01
影响因子：
39.3
通讯作者：
Fox, KM
中科院分区：
文献类型：
--
作者：
Goodall, AH;Curzen, N;Fox, KM
血小板膜上的GPIIb-IIIa复合物是纤维蛋白原的受体，在血栓形成中起重要作用。血小板膜糖蛋白IIIa的基因具有多个等位基因，其中之一，GPIIIa-脯氨酸33（HPA-1 B，pl（A2），ZW（B））等位基因已在一些但不是所有的研究中报道与心肌梗死的风险增加相关。方法和结果来自70名稳定型心绞痛患者（54名男性）的血液样本，其中22名（18名男性）有既往心肌梗死病史，在基因组水平分析了GPIIIa-Leu-Pro 33多态性，以及用于血小板纤维蛋白原结合的全血流式细胞术测量。20例（28.6%）患者（1例纯合子）存在GPIIIa-Pro 33型，代表等位基因频率为0.85和0.15（GPIIIa-Leu 33：Pro 33）。心肌梗死发生率较高GPIIIa-Pro33阳性组与阴性组比较，差异有统计学意义（P < 0.05（32.0%），但这并不显著在所有ADP浓度下，GPIIIa-Pro 33阳性组与ADP刺激的血小板的纤维蛋白原结合均显著高于对照组（P=0.58（0.05）。结论携带Pro 33形式GPIIla的患者血小板增加的趋势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，并主张在闭塞性血管疾病状态中选择性使用抑制ADP介导的血小板活化的治疗剂。
Aims 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 glycoprotein IIIa has multiple alleles one of which, the GPIIIa-Proline33 (HPA-1b, pl(A2), ZW(b)) 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.Methods and Results 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 (0.05).Conclusions 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.