对急性缺血性中风或过渡性缺血性发作的基因多态性和克洛皮多格勒的有效性:系统性审查和元分析
Yuesong Pan1, Weiqi Chen1, Yun Xu1
1From Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, China (Y.P., W.C., X.Z., L.L., Q.Z., G.W., Yongjun Wang, Yilong Wang); China National Clinical Research Center for Neurological Diseases, Beijing (Y.P., W.C., X.Z., L.L., Q.Z., G.W., Yongjun Wang, Yilong Wang); Center of Stroke, Beijing Institute for Brain Disorders, China (Y.P., W.C., L.H., X.Z., L.L., Q.Z., G.W., Yongjun Wang, Yilong Wang); Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease, China (Y.P., W.C., L.H., X.Z., L.L., Q.Z., G.W., Yongjun Wang, Yilong Wang); Department of Epidemiology and Health Statistics, School of Public Health, Capital Medical University, Beijing, China (Y.P.); Beijing Municipal Key Laboratory of Clinical Epidemiology, China (Y.P.); Department of Neurology, Affiliated Drum Tower Hospital of Nanjing University Medical School, China (Y.X.); Department of Neurology, The People's Hospital of Deyang City, China (X.Y.); Department of Neurology, Changhai Hospital, Second Military Medical University, Shanghai, China (Y.H.); Department of Neurology, Xinqiao Hospital, the Third Military Medical University, Chongqing, China (Q.Y.); Department of Neurology, the Second Hospital of Tianjin Medical University, China (X.L.); The First Affiliated Hospital, Jinan University, Guangzhou, China (L.H.); and Dell Medical School, University of Texas at Austin, TX (S.C.J.).
患有缺血性中风或携带CYP2C19功能丧失等位基因的患者在用克洛皮多格勒治疗时面临更高的中风和血管事件风险. 这一遗传因素影响了克洛皮多格勒的疗效,强调了个性化治疗策略的必要性.
科学领域:
- 药物基因组学
- 神经学
- 心血管医学
背景情况:
- 在患有缺血性中风或过渡性缺血性发作 (TIA) 的患者中,克洛皮多格勒的疗效受遗传变异的影响,但研究结果仍然不一致.
- CYP2C19基因型是一个关键的遗传因素,研究其对皮多格勒的反应的影响.
研究的目的:
- 进行系统性审查和元分析,评估基因多态,特别是CYP2C19基因型与中风或TIA患者的克洛皮多格雷尔疗效之间的关联.
- 根据遗传特征评估临床事件的风险,包括中风,复合血管事件和出血.
主要方法:
- 在PubMed和EMBASE进行了全面的文献搜索,截至2016年6月24日.
- 包括的研究重点是用克洛皮多格雷尔治疗的中风或TIA患者,并报告了遗传多态性数据.
- 主要终点是中风,复合血管事件和出血事件.
主要成果:
- 对15项涉及4762名患者的研究分析显示,携带CYP2C19功能丧失等位基因 (* 2, * 3, * 8) 的患者中风风险显著增加 (12. 0%与5. 8%相比;RR,1. 92;P< 0. 001).
- 在这些携带者中,复合血管事件也更频繁 (13. 7% vs 9. 4%; RR, 1.51; P=0. 01),而出血率没有显著差异 (2. 4% vs 3. 1%; RR, 0. 89; P=0. 59).
- 在中风风险方面没有发现显著的异质性,但在复合血管事件方面存在. 在一项研究中,除了PON1,P2Y12和COX-1外,其他遗传变异也显示出有限的关联.
结论:
- 患有缺血性中风或TIA,携带CYP2C19功能丧失等位基因的患者在用克洛皮多格勒治疗时,患中风和复合血管事件的风险更高.
- 这些发现强调了CYP2C19基因型在预测克洛皮多格勒反应和指导治疗决策方面的重要性.
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