用克洛皮多格雷尔治疗中风患者中的CYP2C19变体的药物基因组测试:临床实验室的机会?
Alan H B Wu1, Cody M Orahoske1, Guanmin Chen2
1Department of Laboratory Medicine, University of California, San Francisco, CA, United States.
蒂卡格勒在中风患者中比克洛皮多格雷尔更有效,这些患者具有CYP2C19功能丧失等位基因. 药基因组测试在具有高等位基因频率的种群中具有成本效益.
科学领域:
- 药物基因组学 药物基因组学
- 心血管医学 心血管医学
- 神经学 神经学
背景情况:
- 克洛皮多格雷尔是一种前药物,需要CYP2C19激活才能有效抗血小板.
- CYP2C19功能丧失 (LOF) 基因基因 (*2, *3) 降低了克洛皮多格雷尔在预防心血管事件方面的有效性.
- 提卡格勒勒提供了一个与CYP2C19代谢独立的替代性抗血小板疗法.
研究的目的:
- 评估提卡格雷勒与克洛皮多格雷尔在中国轻度中风和CYP2C19 LOF等位基因的患者中的疗效.
- 分析不同祖先的药基因组测试政策和CYP2C19 LOF等位基因频率.
主要方法:
- 对高风险患者急性非致残性脑血管事件 (CHANCE2) 试验中的克洛皮多格雷尔的审查.
- 在CHANCE2试验出版后对临床实验室药基因组测试政策的分析.
- 在各种祖先种群中对CYP2C19 LOF等位基因频率进行表化.
主要成果:
- 在CHANCE2试验中,在具有CYP2C19 LOF等位基因的患者中,与克洛皮多格雷尔相比,提卡格雷勒治疗的复发性中风减少了1.6%.
- 在太平洋岛屿和亚洲人群 (包括汉族人) 中,CYP2C19 LOF等位基因的频率最高.
- 在欧洲,拉丁裔和西班牙裔拉丁裔人群中观察到较低的CYP2C19 LOF等位基因频率.
结论:
- 对CYP2C19变体的药基因组测试在具有较高LOF等位基因频率的种群中更具经济可行性.
- 在临床实验室环境中,限制基于人群等位基因频率的药物基因组测试在伦理上是有问题的.
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