Relative impact of covariates in prescribing warfarin according to CYP2C9 genotype
Relative impact of covariates in prescribing warfarin according to CYP2C9 genotype
复制标题
DOI：
10.1097/01.fpc.0000114760.08559.dc
复制
发表时间：
2004-08-01
期刊：
影响因子：
--
通讯作者：
Burmester, JK
中科院分区：
文献类型：
--
作者：
Hillman, MA;Wilke, RA;Burmester, JK
接受华法林抗凝治疗的患者维持剂量差异很大。与具有野生型等位基因（*1）的患者相比，具有细胞色素P450 2C 9基因变体（*2和 *3）的患者需要减少的维持剂量。许多其他临床因素也被证明会影响华法林剂量。为了确定CYP 2C 9基因型、年龄、性别、体表面积、合并用药、治疗适应症和合并症的相对影响，我们对453例患者进行了一项回顾性队列研究，这些患者由一个大型的、横向整合的、多专业组实践的抗凝服务管理。在这一主要为白人的患者人群中，*1/*1、*1-2、*1-3、*2-2、*2/*3和 *3/*3的CYP 2C 9基因频率分别为65.1%、19.0%、12.1%、1.6%、1.8%和0.4%，接近Hardy-Weinberg平衡。这些基因型的平均维持剂量分别为36.5、29.1、23.5、28.0、18.1和5.5 mg/周。在单变量分析中，基因型单独占维持剂量变异性的19.8%。年龄、体表面积和男性分别占14.6%、7.5%和4.7%，而作为华法林适应症的心脏瓣膜置换术占变异的5.4%。根据多元回归，这些因素共同占所有给药变异性的33.7%。这些结果将有助于加强数学模型，目前正在开发的前瞻性基因为基础的华法林剂量。(C)2004年利平科特威廉姆斯威尔金斯。
Patients on warfarin anticoagulant therapy demonstrate wide variation in maintenance dose. Patients possessing variants (*2 and *3) of the cytochrome P450 2C9 gene require reduced maintenance doses compared to those having wild-type alleles (*1). Many other clinical factors have been shown to affect warfarin dose as well. To determine the relative impact of CYP2C9 genotype, age, gender, body surface area, concomitant medication, treatment indication and comorbidity, we conducted a retrospective cohort study in 453 patients managed by the anticoagulation service of a large, horizontally integrated, multispecialty group practice. In this largely Caucasian patient population, the CYP2C9 gene frequencies for *1/*1, *1-2, *1-3, *2-2, *2/*3 and *3/*3 were 65.1%, 19.0%, 12.1%, 1.6%, 1.8% and 0.4%, respectively, approximating Hardy-Weinberg equilibrium. Mean maintenance doses for these genotypes were 36.5, 29.1, 23.5, 28.0,18.1 and 5.5 mg/week, respectively. In univariate analyses, genotype alone accounted for 19.8% of the variability in maintenance dose. Age, body surface area and male gender accounted for 14.6%, 7.5% and 4.7%, respectively, while cardiac valve replacement as the indication for warfarin accounted for 5.4% of the variability. Collectively, these factors accounted for 33.7% of all dosing variability according to multiple regression. These results will help strengthen the mathematical models that are currently being developed for prospective gene-based warfarin dosing. (C) 2004 Lippincott Williams Wilkins.