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目的:研究中国汉族患者细胞色素P450(CYP)2C9基因多态性和年龄对华法林剂量的影响,以利于其剂量的调整。方法:2008年4月至2009年3月在首都医科大学附属北京友谊医院服用华法林达稳定状态的住院患者161例纳入研究。患者被分为2组:老年组和成年组。老年组男55例,女45例,平均年龄(72±6)岁;成年组男34例,女27例,平均年龄(49±8)岁。记录患者所服用的华法林剂量、国际标准化比值(INR)、发生抗凝过量和出血的病例、抗凝治疗达稳定剂量-效应关系的时间;应用ABI3700DNA测序仪检测2组患者CYP2C9基因型,比较不同基因型和不同年龄患者华法林的维持剂量、治疗初始阶段抗凝过量发生率、出血发生率以及达稳定剂量-效应关系的时间。结果:2组患者CYP2C9AA基因型和AC基因型分布差异无统计学意义(P>0.05)。AC型患者华法林维持剂量明显低于AA型患者[(2.40±0.96)mg比(2.73±0.65)mg,P<0.01];在AA和AC型患者中,老年组患者华法林维持剂量均明显低于成年组患者[(2.47±0.48)mg比(3.24±0.85)mg,(2.08±0.71)mg比(2.72±1.04)mg,均P<0.01]。华法林治疗初始阶段,AC型患者抗凝过量发生率明显高于AA型患者(35.0%比5.7%,P<0.01);在AA型患者中,老年组患者抗凝过量发生率明显高于成年组(9.3%比0,P<0.05)。AC型患者出血发生率明显高于AA型患者(30.0%比5.0%,P<0.05);在AA型患者中,老年组患者出血发生率明显高于成年组(8.1%比0,P<0.05)。AC型患者应用华法林达稳定剂量-效应关系的时间明显长于AA型患者[(21.4±3.2)d比(10.0±3.5)d,P<0.01],相同基因型老年组与成年组患者达稳定剂量-效应关系的时间比较差异无统计学意义。结论:中国汉族患者CYP2C9基因型和年龄均可影响华法林的治疗剂量,CYP2C9基因多态性的检测结果可作为指导华法林剂量的依据。
Objective: To study the effects of CYP 2C9 gene polymorphism and age on the dosage of warfarin in Chinese Han patients in order to facilitate the dose adjustment. Methods: From April 2008 to March 2009, 161 inpatients with stable warfarin were enrolled in Beijing Friendship Hospital, Capital Medical University. Patients were divided into two groups: the elderly group and the adult group. The elderly group of 55 males and 45 females, mean age (72 ± 6) years; adult group of 34 males and 27 females, mean age (49 ± 8) years old. The warfarin dose, international normalized ratio (INR), anticoagulant and hemorrhage cases, anticoagulant therapy time to stable dose-response relationship were recorded. The CYP2C9 genotypes of two groups were detected by ABI 3700 DNA sequencer, The warfarin maintenance dose, the incidence of anticoagulation over the initial treatment period, the incidence of bleeding, and the time to stable dose-response relationship were compared between patients of different genotypes and at different ages. Results: There was no significant difference in the distribution of CYP2C9AA genotype and AC genotype between the two groups (P> 0.05). Warfarin maintenance dose in AC patients was significantly lower than that in AA patients [(2.40 ± 0.96) mg vs (2.73 ± 0.65) mg, P <0.01]; in AA and AC patients, warfarin maintenance dose (2.47 ± 0.48) mg (3.24 ± 0.85) mg, (2.08 ± 0.71) mg (2.72 ± 1.04) mg, all P <0.01 in the adult group. In the initial stage of warfarin treatment, the incidence of anticoagulation in AC patients was significantly higher than that in AA patients (35.0% versus 5.7%, P <0.01). In AA patients, the incidence of anticoagulation was significantly higher in elderly patients Adult group (9.3% vs 0, P <0.05). The incidence of bleeding in patients with AC was significantly higher than those in patients with AA (30.0% vs. 5.0%, P <0.05). In AA patients, the incidence of bleeding in elderly patients was significantly higher than that in adults (8.1% vs 0, P <0.05 ). The time to stable dose-effect relationship of warfarin in AC patients was significantly longer than that in AA patients [(21.4 ± 3.2) d vs (10.0 ± 3.5) d, P <0.01]. Patients with the same genotype in the elderly and adult patients reached There was no significant difference in the time of stable dose-response relationship. CONCLUSION: The CYP2C9 genotype and age in Chinese Han patients may affect the warfarin dose, and the detection results of CYP2C9 gene polymorphism may serve as a guideline for warfarin dose.