广州地区CYP2C9/VKORC1基因多态性及行个体化治疗患者凝血指标的改变  

Influence of CYP2C9/VKORC1 polymorphisms on coagulation indexes from patients treated with warfarin in Guangzhou area

作　　者：李国豪[1] 杨娜[2] 明凯华[2] 梁丽华[2] 雷秀霞[2] LI Guo-hao YANG Na MING Kai-hua LIANG Li-hua LEI Xiu-xia(Department of Pharmacy Department of Laboratory Investigation, Guangzhou First People＇s Hospital, Guangdong Guangzhou 510l80, China)

机构地区：[1]广州市第一人民医院药剂科,广东广州510180 [2]广州市第一人民医院检验科,广东广州510180

出　　处：《中国医院药学杂志》2016年第21期1894-1897,共4页Chinese Journal of Hospital Pharmacy

摘　　要：目的：调查广州地区汉族人群与华法林代谢相关的CYP2C9/VKORC1基因多态性分布特征,并了解经验用药患者与根据基因型进行个体化抗凝治疗患者凝血指标（TT、PT、PT-INR、FIB）的改变。方法：选取2015年1月至12月住院或门诊676例患者,采用基因芯片法进行CYP2C9/VKORC1基因多态性检测,分析基因型频率和等位基因频率,了解广州地区汉族人群CYP2C9/VKORC1基因多态性分布特征和凝血情况。随机选取初期2.5~3 mg·d-1经验用药组（A组）服用华法林患者91例;经验用药一段时间后进行了CYP2C9/VKORC1基因多态性检测,并根据基因型行个体化用药（B组）。2组患者均按要求定期检测凝血指标。结果：广州地区汉族人群CYP2C9/VKORC1基因型＊1＊1/AA占74.567%;＊1＊1/GA占16.57%;＊1＊3/AA占6.21%;＊1＊3/GA和＊1＊1/GG各占1.18%;＊1＊2/AA和＊1＊3/AA各占0.15%。凝血指标（TT、PT、PT-INR、FIB）A组依次为（13.97±1.43）s、（16.74±8.34）s、（1.47±0.77）INR、（3.34±0.90）s,B组依次为（13.76±1.17）s、（21.71±11.40）s、（1.96±0.90）INR、（3.63±0.92）s;经配对资料t检验,TT2组间无显著差异（P〉0.05）;PT和PT-INR2组间均有非常显著差异（P〈0.01）;FIB A组与B组间有显著差异（P〈0.05）。A组、B组患者在治疗过程中PTINR控制在2~3 INR抗凝治疗理想范围的分别占13.6%和23.57%,经χ2检验有显著差异（P〈0.05）。结论：广州地区汉族人群CYP2C9/VKORC1呈基因多态性,因此华法林按传统经验用药抗凝治疗模式存在一定的盲目性和潜在的危险性,以基因为导向的个体化抗凝治疗为临床在调整华法林抗凝治疗方案提供了科学依据,减少不良事件的发生率。OBJECTIVE To investigate distribution of CYP2C9/VKORC1 polymorphisms related to warfarin metabolism in Han Patients in Guangzhou and changes of coagulation indexes including TT,PT,PT-INR and FIB.METHODS CYP2C9/VKORC1 genotypes were determined by gene chips in 676 inpatients/outpatients from January to December in 2015,and gene polymorphisms and coagulation functions were investigated.Group A included 91 patients to whom warfarin was administered initially at 2.5 to 3 mg·d-1 and then warfarin dose was adjusted by doctors’ experiences.Group B included 91 patients to whom the dose of warfarin was adjusted by genotypes of patients.Coagulation indexes were tested between these two groups regularly.RESULTS The genotype frequencies of CYP2C9/VKORC1 were 74.57%,16.57%,6.21%,1.18% and 1.18%in＊1＊1/AA,＊1＊1/GA,＊1＊3/AA,＊1＊3/GA,＊1＊1/GG genotypes,respectively.Coagulation indexes including TT,PT,PT-INR and FIB were（13.97±1.43）s,（16.74±8.34）s,（1.47±0.77）INR,（3.34±0.90）s in group A,and（13.76±1.17）s,（21.71±11.40）s,（1.96±0.90）INR,（3.63±0.92）s in group B.No statistical difference was observed between two groups for TT by student’s t-test（P〉0.05）.However,statistical difference was observed between two groups for PT（P〈0.01）,PTINR（P〈0.01）and FIB（P〈0.05）.Frequencies of PT-INR in target value from2 to 3 were 13.60% and 23.57%（P〈0.05 by chi-square test）,respectively.CONCLUSION Because of polymorphisms of CYP2C9/VKORC1 of Han Patients in Guangzhou,individual anticoagulant therapy adjusted by genotypes is more scientific than empirical therapy adjusted by experiences.By using the individual anticoagulant therapy,doctors can reduce probabilities of adverse reactions of warfarin.

关 键 词：CYP2C9/VKORC1 基因多态性 个体化治疗 华法林 凝血指标 

分 类 号：R394.3[医药卫生—医学遗传学] R973.2[医药卫生—基础医学]