一名59岁的女性患者患有深静脉血栓形成（DVT）和肺栓塞（PE），每天一次使用6mg华法林作为抗凝剂。在服用华法林之前,她的国际标准化比率(INR)为0.98.华法林治疗后两天,她的INR与基线相比没有变化.由于PE的严重程度高，患者需要迅速达到目标范围（INR目标=2.5，范围=2~3），因此，华法林的剂量从每天6毫克增加到每天27毫克。然而,患者的INR没有随着剂量的增加而改善，仍然保持0.97-0.98的INR。我们在服用27毫克华法林前半小时抽取了血样，并检测到以下基因的单核苷酸多态性，经鉴定与华法林耐药相关：CYP2C9rs1799853，rs1057910，VKORC1rs9923231，rs61742245，rs7200749，rs55894764，CYP4F2rs2108622和GGCXrs2592551。华法林给药2天后，华法林的谷血浆浓度为196.2ng/mL，远低于华法林的治疗药物浓度范围（500-3,000ng/mL）。基因型结果表明，CYP4F2基因具有rs2108622突变，这可以解释华法林抗性的某些方面。需要进一步的研究来充分表征中国华法林剂量反应的其他药物基因组学或药效学决定因素。
One 59-year-old female patient with deep venous thrombosis (DVT) and pulmonary embolism (PE) was treated with 6 mg warfarin once daily as an anticoagulant. Before taking warfarin, her international normalized ratio (INR) was 0.98. Two days after warfarin treatment, her INR did not change from baseline. Due to the high severity of the PE, the patient needed to reach her target range (INR goal = 2.5, range = 2~3) rapidly, so the dose of warfarin was increased from 6 mg daily to 27 mg daily. However, the patient\'s INR did not improve with the dose escalation, still maintaining an INR of 0.97-0.98. We drew a blood sample half an hour before administering 27 mg warfarin and detected single nucleotide polymorphism for the following genes, which were identified to be relevant with warfarin resistance: CYP2C9 rs1799853, rs1057910, VKORC1 rs9923231, rs61742245, rs7200749, rs55894764, CYP4F2 rs2108622, and
GGCX rs2592551. The trough plasma concentration of warfarin was 196.2 ng/mL after 2 days of warfarin administration with 27 mg QD, which was much lower than the therapeutic drug concentration ranges of warfarin (500-3,000 ng/mL). The genotype results demonstrate that the CYP4F2gene has rs2108622 mutation which can explain some aspect of warfarin resistance. Further investigations are necessary to fully characterize other pharmacogenomics or pharmacodynamics determinants of warfarin dose-response in Chinese.
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