Rettie Allan E, Tai Guoying
Department of Medicinal Chemistry, University of Washington, Seattle, WA 98195, USA.
Mol Interv. 2006 Aug;6(4):223-7. doi: 10.1124/mi.6.4.8.
Warfarin, a coumarin anticoagulant, is used worldwide for the treatment and prevention of thromboembolic disease. Warfarin therapy, however, can be difficult to manage because of the drug's narrow therapeutic index and the wide interindividual variability in patient response. It is now clear that genetic polymorphisms in genes influencing metabolism (CYP2C9) and pharmacodynamic response (VKORC1) are strongly associated with warfarin responsiveness. Optimal warfarin dosing in turn drives other positive anticoagulation-related outcomes. Therefore, a strong basic science argument is emerging for prospective genotyping of warfarin patients. Effective clinical translation would establish warfarin pharmacogenomics as a heuristic model for personalized medicine.
华法林是一种香豆素类抗凝剂，在全球范围内用于治疗和预防血栓栓塞性疾病。然而，由于该药物的治疗指数狭窄以及患者反应存在广泛的个体间差异，华法林治疗可能难以管理。现在已经明确，影响代谢的基因（CYP2C9）和药效学反应的基因（VKORC1）中的遗传多态性与华法林反应性密切相关。最佳的华法林剂量反过来又能推动其他与抗凝相关的积极结果。因此，对于华法林患者进行前瞻性基因分型的有力基础科学依据正在形成。有效的临床转化将确立华法林药物基因组学作为个性化医疗的启发式模型。
