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基于群体特异性药物基因组学算法的华法林剂量优化。

Optimization of warfarin dose by population-specific pharmacogenomic algorithm.

机构信息

Department of Clinical Pharmacology and Therapeutics, Nizam's Institute of Medical Sciences, Hyderabad, India.

出版信息

Pharmacogenomics J. 2012 Aug;12(4):306-11. doi: 10.1038/tpj.2011.4. Epub 2011 Mar 1.

Abstract

To optimize the warfarin dose, a population-specific pharmacogenomic algorithm was developed using multiple linear regression model with vitamin K intake and cytochrome P450 IIC polypeptide9 (CYP2C9()2 and ()3), vitamin K epoxide reductase complex 1 (VKORC1()3, ()4, D36Y and -1639 G>A) polymorphism profile of subjects who attained therapeutic international normalized ratio as predictors. New algorithm was validated by correlating with Wadelius, International Warfarin Pharmacogenetics Consortium and Gage algorithms; and with the therapeutic dose (r=0.64, P<0.0001). New algorithm was more accurate (Overall: 0.89 vs 0.51, warfarin resistant: 0.96 vs 0.77 and warfarin sensitive: 0.80 vs 0.24), more sensitive (0.87 vs 0.52) and specific (0.93 vs 0.50) compared with clinical data. It has significantly reduced the rate of overestimation (0.06 vs 0.50) and underestimation (0.13 vs 0.48). To conclude, this population-specific algorithm has greater clinical utility in optimizing the warfarin dose, thereby decreasing the adverse effects of suboptimal dose.

摘要

为了优化华法林剂量,我们采用多元线性回归模型,利用维生素 K 摄入量和细胞色素 P450 IIC 多肽 9(CYP2C9(*)2 和 ()3)、维生素 K 环氧化物还原酶复合物 1(VKORC1()3、()*4、D36Y 和-1639 G>A)多态性,对达到治疗性国际标准化比值的患者进行预测,建立了一种人群特异性的药物基因组算法。新算法通过与 Wadelius、国际华法林药物基因组学联盟和 Gage 算法的相关性进行验证;并与治疗剂量(r=0.64,P<0.0001)相关。新算法的准确性更高(整体:0.89 比 0.51,华法林抵抗:0.96 比 0.77,华法林敏感:0.80 比 0.24),更敏感(0.87 比 0.52)和特异性(0.93 比 0.50)与临床数据相比。它显著降低了高估(0.06 比 0.50)和低估(0.13 比 0.48)的发生率。总之,这种人群特异性算法在优化华法林剂量方面具有更大的临床实用性,从而减少了剂量不足的不良反应。

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