腺二酸盐诱导的血小板聚合与健康受试者的P2Y12基因序列变异有关
Pierre Fontana1, Annabelle Dupont, Sophie Gandrille
1Service d'Hématologie Biologique A, Hôpital Européen Georges Pompidou and Inserm Unité 428, Faculté des Sciences Pharmaceutiques et Biologiques, Université Paris V, Paris, France. pierre.fontana@egp.ap-hop-paris.fr
Circulation
|August 13, 2003
概括
在P2Y12受体的遗传变异影响腺二酸盐 (ADP) 诱导的血小板聚合. 一种特定的P2Y12基因单双型 (H2) 与血小板反应的改变有关,这可能会影响心血管疾病风险和抗血小板药物的疗效.
科学领域:
- 药物基因组学 药物基因组学
- 心血管研究研究心血管研究
- 血小板生物学 血小板生物学
背景情况:
- P2Y12受体是心血管疾病抗血小板治疗的关键标.
- 腺二酸盐 (ADP) 诱导的血小板聚合存在个体间的变异性,但其遗传基础尚不清楚.
研究的目的:
- 调查ADP诱导的血小板聚合的变异性背后的遗传机制.
- 为了确定与血小板聚合表型相关的P2Y12受体基因的序列变异.
主要方法:
- 在98名健康志愿者中检查了ADP诱导的血小板聚合,以确定高响应和低响应者.
- 选了P2Y12基因的序列变异,并确定了常见的多态和单元型 (H1和H2).
- 与最大ADP诱导的血小板聚合和循环腺单酸盐 (cAMP) 水平相关的P2Y12基因单型.
主要成果:
- 确定了两个不同组的受试者具有高和低的ADP诱导的血小板聚合反应.
- 四个频繁的P2Y12多态体处于链接不平衡状态,定义了两个单元类型 (H1和H2).
- P2Y12基因的H2类型与最大的ADP诱导的血小板聚合 (P=0.007) 和更明显的ADP介导的cAMP下调相关.
结论:
- 在健康个体中,P2Y12受体基因的特定单双型 (H2) 与ADP诱导的血小板聚合有关.
- 携带H2单元型的个体可能面临较高的动脉血症风险.
- 携带H2单体型的携带者可能会表现出抑制P2Y12的抗血小板药物的临床有效性降低.
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