Department of Gene Diagnostics and Therapeutics, Research Institute, International Medical Center of Japan, Tokyo, Japan.
Circ J. 2010 May;74(5):977-82. doi: 10.1253/circj.cj-09-0876. Epub 2010 Mar 26.
Warfarin dosing is difficult to establish because of considerable interindividual variation. Thus, warfarin pharmacogenetics have attracted particular interest in relation to appropriate control of anticoagulation.
The 200 eligible subjects were chosen from participants in a hospital cohort. Performance of a pharmacogenetic algorithm recently developed by the International Warfarin Pharmacogenetics Consortium (IWPC) was tested and compared with a clinical algorithm (without genotype data) by calculating the percentage of patients for whom the predicted dose deviated by less than 7 mg/week (1 mg/day) from the actual dose. The pharmacogenetic algorithm accurately identified a significantly (P<0.05) larger proportion of patients to achieve the target international normalized ratio than did the clinical algorithm (68% vs 36% for a low-dose group; and 21% vs 0% for a high-dose group). Also, an increase in warfarin dosage was found to be appropriate for the current status of alcohol drinking (4 mg/week, as against non-drinking) and smoking (3.3 mg/week, as against non-smoking).
The IWPC pharmacogenetic algorithm has clinical application, particularly in identifying Japanese patients who require a low dosage of warfarin and are at greater risk of excessive anticoagulation.
由于个体间存在较大差异，华法林的剂量难以确定。因此，华法林药物遗传学在适当控制抗凝方面引起了特别关注。
从医院队列的参与者中选择了 200 名符合条件的受试者。通过计算预测剂量与实际剂量相差不到 7 毫克/周（1 毫克/天）的患者比例，测试并比较了最近由国际华法林药物遗传学联合会（IWPC）开发的药物遗传学算法与临床算法（无基因型数据）的性能。药物遗传学算法准确地识别出更大比例的患者能够达到目标国际标准化比值，这与临床算法相比具有显著差异（低剂量组为 68%比 36%；高剂量组为 21%比 0%）。此外，还发现对于当前的饮酒（每周增加 4 毫克，而非不饮酒）和吸烟状况（每周增加 3.3 毫克，而非不吸烟），华法林的剂量需要增加。
IWPC 药物遗传学算法具有临床应用价值，特别是在确定需要低剂量华法林且过度抗凝风险较高的日本患者方面。
