Li Jiayi, Wang Shan, Barone Joseph, Malone Brian
P T. 2009 Aug;34(8):422-7.
Warfarin, an anticoagulant, is used to prevent and treat thromboembolic disease. One of the drawbacks of this agent, also known as Coumadin (Bristol-Myers Squibb), is that it is difficult to administer at the correct dose as a result of its narrow therapeutic index, its tendency to cause bleeding, and the individual variability in patient response. Achieving safe and effective doses of warfarin therapy is both an urgent and important concern for many clinicians.Recent research has focused on single-nucleotide polymorphisms (SNPs) of genes that encode two proteins: the cytochrome P450 2C9 enzyme and VKORC1 (vitamin K epoxide reductase complex). Studies suggest that CYP 2C9 influences warfarin metabolism, whereas VKORC1 plays a role in the pharmacodynamic response in expression of the enzymatic target of warfarin. Patients who carry CYP 2C92 and CYP 2C93 alleles tend to require lower warfarin maintenance doses because of their slowed metabolism compared with patients who carry the "wild-type" allele. Patients who carry the VKORC1 A haplotype tend to require lower wafarin maintenance doses as a result of a decreased expression of messenger RNA (mRNA), which produces the proteins necessary for the formation of VKORC1.
华法林是一种抗凝剂，用于预防和治疗血栓栓塞性疾病。这种药物（也称为香豆素，由百时美施贵宝公司生产）的一个缺点是，由于其治疗指数狭窄、有导致出血的倾向以及患者反应存在个体差异，很难给予正确剂量。对许多临床医生来说，实现华法林治疗的安全有效剂量是一个紧迫且重要的问题。最近的研究集中在编码两种蛋白质的基因的单核苷酸多态性（SNP）上：细胞色素P450 2C9酶和维生素K环氧化物还原酶复合体1（VKORC1）。研究表明，CYP 2C9影响华法林的代谢，而VKORC1在华法林酶靶标表达的药效学反应中起作用。与携带“野生型”等位基因的患者相比，携带CYP 2C92和CYP 2C93等位基因的患者由于代谢减慢，往往需要较低的华法林维持剂量。携带VKORC1 A单倍型的患者由于信使核糖核酸（mRNA）表达降低，往往需要较低的华法林维持剂量，而mRNA表达降低会产生形成VKORC1所需的蛋白质。
