细胞色素P4502C9-Leu359基因变异与华法林抗凝治疗研究

目的　研究细胞色素 P45 0 2 C9-Leu3 5 9基因变异与华法林耐量和抗凝出血并发症的关系。方法　对5 5例心脏瓣膜置换术后长期服用华法林的病人 ,根据华法林用量大小分组 :华法林用量 /体表面积≤ 1 .5 mgm2 -1为 G1组 ,>1 .5 mgm2 -1为 G2组。利用 PCR-RFLP法进行 CYP2 C9Leu3 5 9基因测定 ,同时随访出血并发症 ,进行比较分析。结果　G1组 CYP2 C9Leu3 5 9突变明显高于 G2组 (P<0 .0 5 ) ;G1组出血发生率明显高于 G2组 (P<0 .0 5 )。结论CYP2 C9Leu3 5 9突变者 ,华法林耐受剂量小 ;华法林耐量小者 ,容易出血。选择 CYP2 C9Leu3 5 9作为基因监测有助于预测华法林的用量

Importance in the geneticmutation of cytochrome P4502C9 Leu359 in anticoagulation therapy with warfarin.

Objective To analyze the association of mutation in CYP2C9 Leu359 with warfarin dose and the risk of bleeding.Methods and Materials:55 heart valve replacement cases were selected from outpatients in our clinic.With a definite PT/INR,they were divided into two groups according to the index G (G=warfarin dose/body surface area):the patients with G≤1.5mg/m2 were inducted to group 1 or G1,and the one with G>1.5mg/m2 to group 2 or G2.Genotyping for CYP2C9 Ile359 and CYP2C9 Leu359 alleles was done by PCR-RFLP analysis. Results The mutational rate in G1(31.5%) was higher significantly than that in G2(14.71%).P=0.0014.The hemorrhagic rate in G1(31.25%) was higher significantly than that in G2(17.95%).P=0.0249.Conclusions The patients with CYP2C9 Leu359 matation requires less warfarin for efficacious anticoagulation.The patients requireing less warfarin are liable to bleeding.Determine of CYP2C9 Leu359 contributes to anticipate warfarin dosage.