CYP2C9和VKORC1基因多态性对心脏瓣膜置换术后华法林维持剂量和抗凝效果的影响

目的:探讨CYP2C9和VKORC1基因多态性对华法林稳定维持剂量和抗凝治疗的影响,为建立心脏机械瓣膜置换术后患者的华法林个体化给药模型提供依据。方法:应用聚合酶链式反应-限制性片段长度多态性(PCR-RFLP)方法检测福州地区119例心脏机械瓣膜置换术后患者CYP2C9*3、CYP2C9-65G/C和VKORC1-1639A/G基因多态性。收集性别、年龄、体质量信息,同时记录华法林的稳定维持剂量、达标天数,观察抗凝过量、不良反应等指标。结果:CYP2C9*3和CYP2C9-65G/C基因型与低华法林维持剂量相关,VKORC1-1639A/G基因型与高华法林维持剂量相关。CYP2C9杂合体组患者抗凝过量危险性增加,但出血的危险性没有增加;携带CYP2C9和VKORC1突变等位基因的患者,抗凝达稳态时间延长。结论:患者用药前进行CYP2C9和VKORC1基因型检查,预测华法林用药剂量,可减少抗凝过量的发生,缩短剂量调整的时间。

Effects of CYP2C9 and VKORC1 Genetic Polymorphisms on Maintenance Dosage and Anticoagulation Effect of Warfarin in Patients after Undergoing Mechanical Heart Valve Prostheses Replacement

OBJECTIVE：To evaluate the effects of CYP2C9 and VKORC1 gene polymorphisms on maintenance dosage and its anticoagulant effect of warfarin in order to provide evidence for establishing individualized dosage model for patients after undergoing heart mechanical valve replacement. METHODS： Polymerase chain reaction-restriction fragment length polymorphism （PCR-RFLP）method was applied to detect CYP2C9 and VKORC1 receptor gene polymorphisms in 119 patients from Fuzhou after undergoing heart mechanical valve replacement. The indexes such as gender,age,body weight,warfarin maintenance dosage, the time to achieve stable anticoagulation,incidences of over-anticoagulant and adverse reactions were recorded. RESULTS： CYP2C93 and CYP2C9-65G/C genotypes were correlated with low warfarin maintenance dosage but VKORC1-1639A/G geno-type was correlated with high warfarin maintenance dosage. The CYP2C9 heterozygote carriers had an increased risk of over-anticoagulation yet whose risk of bleeding events did not increased. The time to achieve stable anticoagulation was longer in patients who carry CYP2C9 and VKORC1 mutation alleles. CONCLUSIONS：Detection of CYP2C9 and VKORC1 genotypes prior to medication and predicating warfarin dosage may result in lower incidence of over-anticoagulation and reduce the dosage-adjusting time of warfarin.