OBJECTIVE:To investigate the gene polymorphism in CYP 2C9/VKORC1 and individualized medication of warfarin in han population from Zhengzhou , so as provide reference for individualized administration .METHODS:The CYP2C9/VKORC1 genotype of 167 subjects with warfarin ( uncombined with amiodarone ) form Zhengzhou and surrounding area were determined by the polymerase chain reaction -restriction fragment length polymorphism method (PCR-RFLP).And Patients' gender, age, initial dose, stable dose and prothrombin time-international standardized ratio (PT-INR) were recorded.RESULTS:Of the 167 patients, 153 cases (91.62％) were CYP2C91/1, 14 cases (8.38％) were CYP2C91/3, and 0 were CYP2C91/2; 138 cases (82.63％) were VKORC1-1639 AA, 27 cases (16.17％) were VKORC1-1639 AG, and 2 cases ( 1.20％) were VKORC1-1639 GG.The stable dose of patients with VKORC1-1639 GG gene [(5.61 ±0.69)mg/d] and VKORC1-1639 AG gene [(4.01 ±1.05)mg/d] was significantly higher than that of patients with VKORC 1-1639 AA gene [ ( 2.98 ±0.58 ) mg/d ] , with statistically significant difference (P<0.0005).The stable dose of patients with CYP 2C91/1 gene [(3.34 ±0.86)mg/d] was significantly higher than that of patients with CYP 2C91/3 gene [ (2.02 ±0.45) mg/d] , with statistically significant difference (P<0.001).CONCLUSIONS: No significant differences related to the distribution of CYP 2C9/VKORC1 polymorphism in Han population of Zhengzhou and other areas of China .According to gene detection , clinicians can guide patients with individualized administration , not only can avoid risk of bleeding , but can shorten time of getting INR and give early control for the disease .Meanwhile , other factors affected dose of warfarin is essential .%目的:探讨郑州地区汉族人群中华法林代谢相关基因CYP2 C9/VKORC1基因多态性与华法林给药剂量的相关性,为个体化给药提供参考.方法:采用限制性片段长度多态性聚合酶链反应技术,检测167例来自郑州市及其周边地区使用华法林(未联合应用胺碘酮)的患者的CYP2C9/VKORC1基因型,记录患者性别、年龄、初始给药剂量、稳定给药剂量及凝血酶原时间-国际标准化比值(PT-INR).结果:167例患者中,CYP2C91/1基因型者153例(占91.62％),CYP2C91/3基因型者14例(占8.38％),未发现CYP2C91/2型者;VKORC1-1639 AA基因型者138例(占82.63％),VKORC1-1639 AG基因型者27例(占16.17％),VKORC1-1639 GG基因型者2例(占1.20％).VKORC1-1639 GG基因型[(5.61±0.69)mg/d]、VKORC1-1639 AG基因型[(4.01±1.05)mg/d]患者的稳定给药剂量明显高于VKORC1-1639 AA基因型[(2.98±0.58)mg/d],差异均有统计学意义(P<0.0005);CYP2C91/1基因型患者的稳定给药剂量[(3.34±0.86)mg/d]明显高于CYP2C91/3基因型[(2.02±0.45)mg/d],差异有统计学意义(P<0.001).结论:郑州地区汉族人群CYP2C9/VKORC1基因多态性的分布与全国其他地区基本一致,根据基因检测指导患者个体化给药,不仅可以避免出血风险,还可以缩短达到目标INR的时间,可以较早控制病情.同时,不能忽视影响华法林给药剂量的其他因素.
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