急性冠脉综合征患者中糖蛋白Ia基因807 C/T多态性与阿司匹林和氯吡格雷治疗后血小板反应性之间无关联。

Lack of association between the 807 C/T polymorphism of glycoprotein Ia gene and post-treatment platelet reactivity after aspirin and clopidogrel in patients with acute coronary syndrome.

作者信息

Cuisset Thomas, Frere Corinne, Quilici Jacques, Morange Pierre-Emmanuel, Saut Noémie, Romero-Barra Marie, Camoin Laurence, Lambert Marc, Juhan-Vague Irène, Bonnet Jean-Louis, Alessi Marie-Christine

机构信息

Department of cardiology, CHU Timone, Marseille, France.

出版信息

Thromb Haemost. 2007 Feb;97(2):212-7.

DOI:
Abstract

Variability in platelet response to antiplatelet therapy and its clinical relevance have been well described. However, the underlying mechanisms remain unclear. It was the aim of the present study to assess whether the response to aspirin and clopidogrel may be influenced by the 807 C/T polymorphism of the glycoprotein Ia (GpIa) gene in patients with non-ST elevation acute coronary syndrome (NSTE ACS). Six hundred one NSTE ACS patients were included in our study and were divided into three groups: CC homozygotes, CT heterozygotes ad TT homozygotes. All patients received loading doses of 600 mg clopidogrel and 250 mg aspirin at least 12 hours before blood samples were drawn. Post-treatment platelet reactivity was assessed by post treatment ADP 10 microM-induced platelet aggregation (ADP-Ag), VASP phosphorylation (PRI VASP) and P-selectin expression. Non-response to dual antiplatelet therapy was defined by high post-treatment platelet reactivity (HPPR=ADP-Ag > 70%). Significant variability in the distribution of platelet parameters was observed in the overall study population. No significant difference in platelet parameters profiles was observed within patients having the same genotype, for ADP-Ag (p=0.33), PRIVASP (p=0.72) and P-selectin expression (p=0.37). The genotype frequencies of the 807 C/T polymorphism of the GpIa gene were similar in responders and non-responders defined by persistent HPPR (p=0.104). In conclusion, our study did not show any influence of 807 C/T polymorphism of GpIa gene on post-treatment platelet reactivity assessed by ADP-Ag, PRI VASP or P-selectin expression in 601 NSTE ACS patients.

摘要

血小板对抗血小板治疗反应的变异性及其临床相关性已得到充分描述。然而,其潜在机制仍不清楚。本研究的目的是评估非ST段抬高急性冠状动脉综合征(NSTE ACS)患者中,糖蛋白Ia(GpIa)基因807 C/T多态性是否会影响对阿司匹林和氯吡格雷的反应。我们的研究纳入了601例NSTE ACS患者,并将其分为三组:CC纯合子、CT杂合子和TT纯合子。所有患者在采集血样前至少12小时接受600 mg氯吡格雷和250 mg阿司匹林的负荷剂量。通过治疗后10 microM ADP诱导的血小板聚集(ADP-Ag)、VASP磷酸化(PRI VASP)和P-选择素表达来评估治疗后血小板反应性。双重抗血小板治疗无反应定义为治疗后血小板高反应性(HPPR = ADP-Ag > 70%)。在整个研究人群中观察到血小板参数分布存在显著变异性。对于ADP-Ag(p = 0.33)、PRI VASP(p = 0.72)和P-选择素表达(p = 0.37),在具有相同基因型的患者中未观察到血小板参数谱的显著差异。由持续性HPPR定义的反应者和无反应者中,GpIa基因807 C/T多态性的基因型频率相似(p = 0.104)。总之,我们的研究未显示GpIa基因807 C/T多态性对601例NSTE ACS患者中通过ADP-Ag、PRI VASP或P-选择素表达评估的治疗后血小板反应性有任何影响。

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