摘要
目的评价细胞色素P450酶2C9(CYP2C9)及维生素K环氧化物还原酶复合体亚单位1(VKORC1)基因多态性对中国肺栓塞患者华法林初始抗凝疗效的影响。方法初次服用华法林抗凝的中国肺栓塞患者95例,用TaqMan MGB探针法,检测CYP2C9*2、*3位点和VKORC1-1639A>G位点基因型。记录患者的年龄、性别、体重、身高、服用华法林后每次INR值等指标,并记录患者从服用华法林开始到INR首次达标的时间、INR首次达标时华法林总剂量和日平均剂量等指标。结果 VKORC1-1639AG/GG基因型患者比VKORC1-1639AA基因型患者INR首次达标时间明显延长(P<0.001),且INR首次达标时所服用的华法林总剂量和日均剂量均高于后者(P<0.001);CYP2C9*2或*3变异的患者在初始抗凝阶段发生INR超过治疗窗(INR>3)的比例较高。患者性别、年龄、体重、CYP2C9和VKORC1基因型等因素在内的华法林初始剂量预测模型可解释54.6%左右的华法林剂量个体差异(R2=0.546,P<0.001)。结论 CYP2C9和VKORC1基因型检测对指导中国肺栓塞患者初始抗凝阶段个体化应用华法林有一定的临床意义。
Objective To evaluate the effect of CYP2C9 and VKORC1 polymorphisms on the initial response to warfarin in Chinese pulmonary embolism patients.MethodsIn 95 Chinese pulmonary embolism patients starting warfarin therapy whose INR target value is 2.0-3.0,we detected VKORC1 and CYP2C9 gene polymorphisms with TaqMan MGB Probe method,and recorded the indexes such as gender,age,body weight and height,each INR values after taken warfarin.The study outcomes were the time to the first INR reach target value,the total warfarin doses and average daily dose when INR first reached target value.ResultsPatients carrying VKORC1-1639A/G or G/G had increased time to the first INR reach target value（P〈0.001）;and the total warfarin doses and average daily dose when INR first reached target value were higher than those of wild-type VKORC1-1639A/A carriers（P〈0.001）;CYP2C9＊1/＊3 or ＊1/＊2 carriers had higher percentage of occurrence INR3 than CYP2C9＊1/＊1 carriers;warfarin initial dose algorithm including gender、age、weight、VKORC1 and CYP2C9 gene polymorphisms,could explain about 54.6% individual dose requirement （R2=0.546,P0.001）.ConclusionCYP2C9 and VKORC1 polymorphisms had clinical significance to guide the individualized warfarin dosage in Chinese pulmonary embolism patients.
出处
《中国临床药理学杂志》
CAS
CSCD
北大核心
2012年第4期256-259,共4页
The Chinese Journal of Clinical Pharmacology
基金
国家科技重大专项基金资助项目(2008ZX09312-018
2011ZX09304
2012ZX09303008-001)
