华法林个体化剂量与CYP2C9/VKORC1基因组之间的关系

Investigation of the Relationship between the Individual Warfarin Dosing and the Pharmacogenomics

目的建立一个适合福建汉族人群的华法林给药模型,指导华法林个体化抗凝治疗。方法通过PCR-杂交技术对口服华法林抗凝患者进行细胞色素氧化酶P450 2C9*1/*3(CYP2C9*1/*3)、维生素K环氧化物还原酶复合体亚单位1-1639A/G(VKORC1-1639A/G)基因分型,收集患者年龄、性别、身高、体质量及华法林稳态剂量信息。结果通过多元线性分析推导出华法林稳态给药剂量公式,建立的多元线性回归的模型中包含年龄、体质量指数、CYP2C9*1/*3和VKORC1-1639A/G基因型,该模型能解释约21.2%个体间华法林剂量差异。结论获得的基于临床和药物基因组学的华法林稳态剂量公式,一定程度上提高了华法林使用的安全性,将有助于口服华法林达到更安全的稳态剂量。

Objective To investigate a possible warfarin dosing model to guide the individualized therapeutic anticoagulation with warfarin in Fujian Han population . Methods The PCR‐hybridization was used for genotyping of Cytochrome P450 2C9＊1/＊3（CYP2C9＊1/＊3） and vitamin K epoxide reductase complex subunit 1‐1639‐A/G （VKORC1‐1639‐A/G） in patients taking oral warfarin anticoagulation . We collected the patients’ clinical information including age ,gender ,height ,weight and stable warfarin dose . Results The warfarin dose predicting formula is deduced by the analysis of the multiple linear regres‐sion . The established multiple linear regression model , which contained age , body mass index , CYP2C9＊1/＊3 and VKORC1‐1639‐A/G genotype ,could explain the inter‐individual difference in warfarin dose about 21 .2% -20 .9% . Conclusion The warfarin dosing formula based on clinical and pharmacog‐enomics will help to effectively improve the clinical safety of warfarin anticoagulation .