三种华法林基因预测模型与心脏瓣膜置换术后华法林剂量的相关性研究  

A Correlation Study of Three Warfarin Pharmacokinetic Dosing Algorithms Models and Warfarin Dose after Cardiac Valve Replacement

作　　者：彭齐[1] 陶凉[1] 陈晓英[1] 胡大清[1] 

机构地区：[1]武汉亚洲心脏病医院心脏外科,武汉430022

出　　处：《解放军医药杂志》2014年第12期28-32,共5页Medical & Pharmaceutical Journal of Chinese People’s Liberation Army

基　　金：武汉市卫生局科研项目(WX13B28)

摘　　要：目的研究湖北地区汉族人细胞色素P450(CYP)2C9基因和维生素K环氧化物还原酶复合体1(VKORC1)基因型;评估3种不同华法林剂量预测模型与其剂量的相关性。方法收集我院收治的心脏瓣膜置膜术后应用华法林的108例患者并获取华法林稳态剂量,采用聚合酶链反应-限制性内切酶片段长度多态性(PCRRFLP)技术检测CYP2C9和VKORC1基因型。比较3种基因预测模型结果与实际华法林稳态剂量的相关性。结果根据基因型判断的华法林用药剂量与稳态剂量相关性更大,同时预测模型3相关性略高于预测模型2。结论在湖北地区汉族人群中,存在CYP2C9和VKORC1基因多态性,且不同基因型患者华法林用量存在差异,预测模型有助于预测华法林稳态剂量。Objective To investigate the genotypes of cytochrome P450 2C9 （CYP2C9） and vitamin K epoxide reductase complex 1 （ VKORCI ） , and to analyze the correlation of three Warfarin pharmaeokinetic dosing algorithms mod- els and Warfarin dose in Han population of Hubei Province. Methods Stable Warfarin doses of 108 inpatients taking Warfarin from March to August 2012 were achieved. Genotypes of CYP2C9 and VKORC1 were detected with polymerase chain reaction-restriction fragment length polymorphism （PCR-RFLP） technique. The correlations of results of three gen- otypes predictive models and stable Warfarin dose were compared. Results Dose determined by genotypes showed more correlation and accuracy, and the correlation of model 3 was more obvious than that of model 2. Conclusion There are polymorphism of CYP2C9 and VKORC1 in Han population of Hubei Province, and there are significant differences in sta- ble Warfarin dosage in patients with different genotypes. Establishment of Warfarin pharmacokinetic dosing algorithms model may be helpful in prediction of Warfarin doses.

关 键 词：华法林 药物剂量计算 基因转变 细胞色素P450酶2C9 维生素K环氧化物还原酶复合体1 

分 类 号：R973.2[医药卫生—药品]