CYP2C9和CYP4F2基因多态性对瓣膜置换术后华法林维持剂量的影响  

Influence of CYP2C9 and CYP4F2 gene polymorphisms on stable warfarin dose after cardiac valve replacement

作　　者：马建新 董兵 马建慧[3] 李胜萍[3] 刘学 

机构地区：[1]解放军305医院干部病房,北京市100017 [2]解放军305医院心胸外科,北京市100017 [3]首都医科大学护理学院分院,北京市100070

出　　处：《实用医学杂志》2017年第7期1120-1123,共4页The Journal of Practical Medicine

基　　金：解放军305医院重点科研基金项目(编号:12YA01)

摘　　要：目的:探讨细胞色素P450酶(CYP2C9和CYP4F2)基因多态性对瓣膜置换术后华法林抗凝强度的影响。方法:选择瓣膜置换术后使用华法林抗凝患者136例,将患者分为4组:CYP2C9野生型组(CYP2C9*1*1)、CYP2C9突变型组(CYP2C9*3)、CYP4F2 rs2108622野生型组(CC)、CYP4F2 rs2108622突变型组(CT或TT),用Taq Man MGB探针法,检测CYP2C9*3位点和CYP4F2 rs2108622位点基因型。记录一般资料,华法林初始剂量和基础国际标准化比率(INR)测定结果,并进行随访;记录初始服用华法林到INR首次达标的时间、华法林达标总用量和平均每日用量。结果:CYP2C9*1*1患者比CYP2C9*3患者INR首次达标时间长、INR首次达标时所需的华法林总量、日均剂量大(P<0.05)。CYP2C9和CYP4F2 rs2108622基因均变异的患者INR首次达标需要的平均时间最短,且INR首次达标时所服用的华法林总剂量和平均日用量最少,与2个基因均无变异组比较,差异有显著性(P<0.05);与只有CYP2C9基因变异患者相比,INR首次达标的平均时间缩短,达标时华法林总用量减少(P<0.05)。结论:CYP2C9和CYP4F2基因多态性是影响华法林维持剂量重要的遗传因素,患者用药前进行CYP2C9和CYP4F2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。Objective To evaluate the influence of cytochrome P450 （CYP2C9 and CYP4F2） polymorphisms on anticoagulant intensity of warfarin after cardiac valve replacement. Methods A total of 136 patients taking warfarin after cardiac valve replacement were identified and classified into 4 groups： CYP2C9 wild type group （CYP2C9＊1＊1） , CYP2C9 mutated type group （CYP2C9＂3） , CYP4F2 rs2108622 wild type group （CC） and CYP4F2 rs2108622 inutated type group （CT or TT）. The patients＇ baseline data, initial dose of warfarin and base INR measurement results were recorded and then the follow-up was conducted. The initial administration of warfarin to INR standard time for the first time, total amount of warfarin and the average daily amount were recorded. Results Patients carrying CYP2C9＊ 1＊1 had increased time to reach INR target value for the first time （P 〈 0.05 ） ; and the total warfarin doses and average daily dose when INR reached target value were higher than those carrying CYP2C9＊3 （P 〈 0.05）. When compared with those in two wild type groups, patients carrying CYP2C9 and CYP4F2 rs2108622 mutated type needed the shortest time when INR reached target value for the first time, and the total warfarin doses and average daily dose when INR first reached target value was the lowest, which shnwed significant difference （P 〈 0.05）. And when compared with CYP2C9 mutated type group, the INR average time to reach the first target was shortened and the total warfarin dose of patients carrying CYP2C9 and CYP4F2 rs2108622 mutated type was lower （P 〈 0,05）. Conclusion The gene polymolq0hisms of CYP2C9 and CYP4F2 are significant hereditary factors influencing warfarin dose. Detection of CYP2C9 and CYP4F2 genotypes prior to medication and predicating warfarin dosage may result in lower incidence of over-antieoagulation and reduce the dosage-adjusting time of warfarin.

关 键 词：瓣膜置换 华法林 细胞色素P450酶 基因多态性 

分 类 号：R654.2[医药卫生—外科学]