对ADCY9基因型对Anacetrapib反应的影响
Jemma C Hopewell1, Maysson Ibrahim1, Michael Hill1,2
1Clinical Trial Service Unit and Epidemiological Studies Unit (J.C.H., M.I., M.H., L.B., M.J.L., R.C.), Nuffield Department of Population Health, University of Oxford, United Kingdom.
Circulation
|July 24, 2019
概括
这项研究没有发现基于ADCY9基因型的胆固醇转移蛋白 (CETP) 抑制剂anacetrapib在动脉样硬化血管疾病患者中的有效性有显著差异. ADCY9基因型似乎不会对阿纳塞特拉皮产生重大影响.
科学领域:
- 心血管医学
- 药物遗传学
- 遗传学
背景情况:
- 探索性分析表明ADCY9基因型与胆固醇转移蛋白 (CETP) 抑制剂治疗的反应之间存在联系.
- 在REVEAL试验中,CETP抑制剂阿纳塞特拉皮在动脉样硬化血管疾病患者的临床疗效得到了证明.
研究的目的:
- 在REVEAL试验中研究ADCY9基因型对阿纳塞特拉皮的反应的影响.
- 确定ADCY9基因型是否影响动脉样硬化血管疾病患者的阿纳塞特拉皮的临床疗效.
主要方法:
- 在REVEAL试验中使用了随机的,安慰剂控制的设计.
- 患有稳定的动脉样硬化血管疾病的参与者同时接受了阿纳塞特拉皮或安慰剂强化治疗.
- 考克斯比例危险模型分析了阿纳塞特拉皮布分配及其与ADCY9 rs1967309基因型对主要血管事件的影响.
主要成果:
- 不同的ADCY9基因型 (GG,AG,AA) 之间没有观察到对Anacetrapib的主要血管事件的比例减少的显著差异.
- 对相互作用的基因型P值为0. 96,表明没有统计学上显著的药物遗传效应.
- 没有发现ADCY9基因型与特定血管事件成分或脂质反应的减少.
结论:
- REVEAL试验是迄今为止关于这种药物遗传相互作用的最大研究,它没有支持ADCY9基因型与anacetrapib的临床作用相关的假设.
- 需要进行进一步的研究,例如正在进行的dal-GenE研究,以确认与dalcetrapib等其他CETP抑制剂的潜在药物遗传相互作用.
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