在心脏门手术后的患者中,基因多态和初始华法林治疗之间的关联
Zhaohui Liu1, Fengming Luo1, Juan Zhao1
1Department of Laboratory Medicine, State Key Laboratory of Cardiovascular Disease, Beijing Key Laboratory for Molecular Diagnostics of Cardiovascular Diseases, Center of Laboratory Medicine, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
在CYP2C9,VKORC1和GGCX的基因变异在早期华法林治疗中显著影响国际正常化比率 (INR) 的变化. 术前遗传测试可以指导心脏门手术患者的最初华法林剂量.
科学领域:
- 药物基因组学 药物基因组学
- 心血管外科心血管外科
- 血栓事件管理的管理.
背景情况:
- 华法林是预防和治疗血栓事件的关键抗凝剂.
- 对华法林治疗的个体反应可能会有很大差异.
- 了解遗传影响是优化早期华法林治疗的关键.
研究的目的:
- 为了研究基因多态化对华法林治疗早期阶段的影响.
- 分析特定基因型与心脏门手术后患者的华法林治疗结果之间的关系.
- 为了确定预测华法林反应和变异性的遗传标记.
主要方法:
- 使用微阵列芯片对九个单核酸多态 (SNP) 的基因定型.
- 将患者分为正常,敏感和高度敏感的响应者.
- 评估治疗范围 (TTR) 和国际规范化比率 (INR) 的时间变化.
- 应用通用线性回归模型来分析影响因素.
主要成果:
- 确定了诸如CYP2C9*3,CYP2C19*3,CYP2C19*17和VKORC1-1639G>A之类的关键变异的流行情况.
- 敏感性分组显著影响了INR变异性,敏感组的变异性更高.
- 在CYP2C9*3,VKORC1-1639G>A和GGCX-3261G>A中显示出与INR变异性的显著关联.
- 在基因多态和TTR.之间没有发现显著的关联.
结论:
- 在最初的华法林治疗期间,CYP2C9,VKORC1和GGCX基因型显著影响INR变异性.
- TTR与研究的基因多态性没有显著的关联.
- 临床关注INR变异性至关重要,并建议进行手术前遗传查,以优化华法林启动.
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