Ticagrelor yields consistent dose-dependent inhibition of ADP-induced platelet aggregation in patients with atherosclerotic disease regardless of genotypic variations in P2RY12, P2RY1, and ITGB3
Ticagrelor yields consistent dose-dependent inhibition of ADP-induced platelet aggregation in patients with atherosclerotic disease regardless of genotypic variations in P2RY12, P2RY1, and ITGB3
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DOI：
10.1080/09537100903075324
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发表时间：
2009-01-01
期刊：
影响因子：
3.3
通讯作者：
Armstrong, Martin
中科院分区：
文献类型：
--
作者：
Storey, Robert F.;Thornton, S. Melissa;Armstrong, Martin
血小板P2Y12受体是氯吡格雷治疗的靶点，氯吡格雷已被证明可以减少动脉粥样硬化疾病的血栓栓塞并发症，但在反应的可变性和效果的不可逆性方面存在局限性。该受体也是替格瑞洛（AZD6140）的靶点，替格瑞洛是第一种可逆结合的口服P2Y12受体拮抗剂，不需要代谢激活，并且比氯吡格雷治疗产生更一致的血小板聚集抑制。该受体基因（P2RY12）的单核苷酸多态性（snp）已被描述，其中一些与血小板反应性的变异有关。一些研究小组也报道了P2RY1和ITGB3的snp影响血小板对二磷酸腺苷（ADP）的反应性。我们评估了这些基因的snp是否影响了分散研究（稳定性动脉粥样硬化疾病）和分散研究2（非st段抬高急性冠状动脉综合征）患者对替格瑞洛的药效学反应。151例接受替格瑞洛治疗的未使用氯吡格雷的高加索患者的血小板聚集数据（基线和4周）和DNA样本。对3个基因内的74个snp进行基因分型。经过多次比较调整后，没有发现这些snp显著影响替格瑞洛对adp诱导的血小板聚集的抑制作用。
The platelet P2Y12 receptor is the target of clopidogrel therapy, which has been shown to reduce thromboembolic complications of atherosclerotic disease but has limitations in terms of variability of response and irreversibility of effect. This receptor is also a target for ticagrelor (AZD6140), the first reversibly binding oral P2Y12 receptor antagonist that does not require metabolic activation and yields more consistent inhibition of platelet aggregation than clopidogrel therapy. Single nucleotide polymorphisms (SNPs) have been described in the gene for this receptor (P2RY12), some of which have been associated with variability in platelet reactivity. SNPs in P2RY1 and ITGB3 have also been reported by some groups to affect platelet reactivity to adenosine diphosphate (ADP). We assessed whether SNPs in these genes influenced the pharmacodynamic response to ticagrelor in patients enrolled in both the DISPERSE study (stable atherosclerotic disease) and the DISPERSE2 study (non-ST-segment elevation acute coronary syndromes). Platelet aggregation data (at baseline and 4 weeks) and DNA samples from clopidogrel-naive Caucasian patients treated with ticagrelor were available for 151 patients. Seventy four SNPs within three genes were genotyped. After adjustment for multiple comparisons, none of these SNPs were found to significantly influence inhibition of ADP-induced platelet aggregation by ticagrelor.