摘要
目的:评价中国汉族人群临床特征及基因型对华法林剂量的影响,并构建华法林给药模型,为临床华法林个体化给药提供参考。方法:按照设定标准选取某医院2011年1月至2013年10月行心脏瓣膜手术后接受华法林抗凝治疗并达到华法林稳定剂量的中国汉族人群203例,对纳入人群进行CYP2C9*3、VKORC1-1639G/A基因多态性检测,结合基因型及患者临床特征,分析对华法林稳定剂量的影响,并采用多元逐步线性回归分析建立数学模型。结果:性别、吸烟、饮酒及高血压病史对华法林剂量无明显影响(P>0.05)。华法林剂量与年龄呈负相关(r=-0.155,P=0.027);与身高、体质量呈正相关(r=0.166、0.190,P=0.009、0.003)。CYP2C9*3、VKORC1-1639G/A基因多态性对华法林剂量的影响在统计学上有统计学差异(P<0.01)。拟合得到华法林给药模型D=2.855-1.173×CYP2C9(AC)+0.020×W-0.024×A+4.064×VKORC1(GG)+1.486×VKORC1(GA)。结论:华法林的剂量受到年龄、身高、体质量及CYP2C9*3、VKORC1-1639G/A基因多态性的影响,依据华法林给药模型可优化华法林个体化给药方案,但仍有待于临床进一步验证。
AIM：To assess the effect of clinical factors and gene polymorphism on stable warfarin dosage in Chinese Han population,then and to establish a dose adjustment model for clinical individualized medication.METHODS：Based on the specified standard,203patients after cardiac valve surgery and taking with stable warfarin dosage treatment in a hospital from January 2011to October 2013 were enrolled in the study.As well,all the patients′CYP2C9＊3,VKORC1-1639G/A genetic polymorphisms were detected by PCR-RELP and sequencing technology.Effects of above-mentioned gene polymorphisms on the dose of warfarin combining with clinical characteristics of patients were analyzed and set up computation model by multiple stepwise regression analysis.RESULTS：There was no significant association between the sexgender,smoking status,drinking status and hypertension history with stable warfarin dosage（P〉 0.05）.The stable dose of warfarin was negatively correlated with age（r=-0.155,P=0.027） and positively correlated with body height and body weight of patients（r=0.166,0.190,P= 0.009,0.003）.There were statistically significance significant in the effect of CYP2C9＊3,VKORC1-1639G/A polymorphisms on the dose of warfarin（P〈0.01）.A medication model D= 2.855-1.173×CYP2C9（AC）＋0.020× W-0.024×A＋4.064×VKORC1（GG）＋1.486× VKORC1（GA）was obtained.CONCLUSION：It shows that age,body height,body weight and CYP2C9＊3,VKORC1-1639G/A genetic polymorphisms have influences on the stable dose of warfarin.Individualized medication of warfarin could be optimized and probably better the individualized medication of warfarin based on the model which needs to be furthermore verified in clinic.
出处
《中国临床药理学与治疗学》
CAS
CSCD
2014年第3期284-290,共7页
Chinese Journal of Clinical Pharmacology and Therapeutics
基金
安徽省"十二五"临床重点专科学科建设基金(01Z35)
皖南医学院弋矶山医院引进人才科研基金资助项目(YR201204)
