摘要
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 investigate the effects of cytochrome P450 （CYP） 2C9 gene polymorphisms and age in Chinese Han patients on warfarin dose in order to benefit warfarin dose adjustment. Methods：Between April 2008 and March 2009,161 inpatients at stabilized status on warfarin therapy from Beijing Friendship Hospital of Capital Medical University entered the study. The patients were divided into the following two groups：the elderly group and the adult group. The elderly group comprised 55 male patients and 45 female patients with average age of （72±6） years. The adult group comprised 34 male patients and 27 female patients with average age of （49±8） years. Warfarin dose,International Normalized Ratio （INR）,cases of overanticoagulation and bleeding,the duration of warfarin treatment achieving the steady dose-effect relationship were recorded. The CYP2C9 gene types in patients in both groups were measured using ABI 3700 DNA sequencer. Maintenance dose of warfarin,the incidence of overanticoagulation in the initiatial period of warfarin treatment,the incidence of bleeding,the time achieving the steady dose-effect relationship were compared between patients with different genotypes and ages. Results：There were no significant differences in distribution of CYP2C9 AA and AC genotypes between the adult and elderly groups （P〈0.05）. The maintenance doses of warfarin were markedly lower in patients with AC genotype than in those with AA genotype [（2.40±0.96） mg vs （2.73±0.65） mg,P〈0.01]; the warfarin maintenance dose in patients with AA and AC genotypes were markedly lower in the elderly group than in the adult group[（2.47±0.48） mg vs （3.24±0.85） mg,（2.08±0.71） mg vs （2.72±1.04） mg,both P〈0.01]. During the initiatial period of warfarin treatment,the incidence rate of overanticoagulation was markedly higher in patients with AC genotype than in those with AA genotype （35.0% vs 5.7%,P〈0.01）; the incidence rate of overanticoagulation in patients with AA genotype w
出处
《药物不良反应杂志》
2010年第4期240-245,共6页
Adverse Drug Reactions Journal
