CYP2C9及CYP2C19基因多态性在非瓣膜性心房颤动患者抗凝治疗中指导作用分析  

Analysis of the guiding role of CYP2C9 and CYP2C19 gene polymorphisms in anticoagulation therapy in patients with nonvalvular atrial fibrillation

作　　者：周虹 谢飞 华阳 吉顺莉[3] 陆洋 ZHOU Hong;XIE Fei;HUA Yang;JI Shunli;LU Yang(Department of Pharmacy,Haian People's Hospital,Haian 226600,China)

机构地区：[1]海安市人民医院药剂科,226600 [2]海安市人民医院心血管内科,226600 [3]南通大学附属医院药学部

出　　处：《心肺血管病杂志》2023年第12期1212-1218,共7页Journal of Cardiovascular and Pulmonary Diseases

基　　金：南通市基础科学研究和社会民生科技计划项目(JCZ2022010)。

摘　　要：目的:探究CYP2C9,CYP2C19基因多态性在非瓣膜性心房颤动患者抗凝治疗中的指导作用。方法:收集我院于2021年11月至2022年11月收治的非瓣膜性心房颤动患者202例临床资料,按照基因多态性检测结果分组治疗,将CYP2C9*1*1合并CYP2C19*1*1常规治疗的患者作为对照组,CYP2C9*3、CYP2C19*2、CYP2C19*3基因指导下的个体化治疗的患者为观察组。比较患者一般资料、华法林起效时间、起效剂量、平均剂量、INR达标时间、凝血因子Ⅱ、Ⅶ、Ⅸ、Ⅹ活性、不良事件发生情况。多元线性回归分析抗凝剂量的影响因素。结果:CYP2C9*1*1、CYP2C9*3发生率分别为88.4%、11.6%,CYP2C19*1*1、CYP2C19*2、CYP2C19*3发生率分别为68.5%、23.8%、7.6%,CYP2C9*3合并CYP2C19*2/CYP2C19*3、CYP2C9*1*1合并CYP2C19*1*1发生率分别为1.3%、67.2%。其中对照组占比60.6%,观察组占比39.4%。两组年龄、性别、高血压、高血脂、糖尿病、冠心病、BMI、饮酒、吸烟比较,差异无统计学意义(P>0.05)。观察组华法林起效时间、起效剂量、平均剂量、INR达标时间均显著低于对照组(P<0.05)。观察组凝血因子Ⅱ、Ⅶ、Ⅸ、Ⅹ活性显著高于对照组(P<0.05)。两组不良事件发生情况比较,差异有统计学意义(P>0.05)。CYP2C9*1抗凝剂量显著高于CYP2C9*3,CYP2C19*1抗凝剂量显著高于CYP2C19*2/CYP2C19*3,≥70岁患者抗凝剂量显著低于<70岁患者,BMI≥25 kg/m2患者抗凝剂量显著高于BMI<25 kg/m2患者(P>0.05)。将抗凝剂量作为因变量,CYP2C9、CYP2C19基因分型、年龄、BMI作为自变量进行多元线性回归分析,结果显示,CYP2C9*3、CYP2C19*2、CYP2C19*3、BMI≥25 kg/m2为华法林抗凝剂量的危险因素,年龄<70岁为保护因素,年龄与抗凝剂量呈负相关关系,BMI与抗凝剂量呈正相关关系。Log(P)=0.520×CYP2C9*3+0.225×CYP2C19*2+0.293×CYP2C19*3-0.160×年龄+0.394×BMI+4.522。结论:CYP2C9,CYP2C19基因多态性的检测能够对非瓣膜性心房颤动患者抗凝�Objective:To explore the guiding role of CYP2C9 and CYP2C19 gene polymorphisms in anticoagulation therapy of patients with nonvalvular atrial fibrillation.Methods:Clinical data of 202 patients with non-valvular atrial fibrillation treated in our hospital from November 2021 to November 2022 were collected and grouped according to the results of gene polymorphism detection.Patients treated with CYP2C9*1*1 combined with CYP2C19*1*1 conventional treatment were selected as the control group.Patients receiving individualized therapy under the guidance of CYP2C9*3,CYP2C19*2 and CYP2C19*3 genes were the observation group.General data,warfarin onset time,onset dose,average dose,INR reaching time,activity of coagulation factorsⅡ,VII,IX andⅩ,and occurrence of adverse events were compared.The influence factors of anticoagulant dose were analyzed by multiple linear regression.Results:The incidence rates of CYP2C9*1*1 and CYP2C9*3 were 88.4%and 11.6%,respectively.The incidence rates of CYP2C19*1*1,CYP2C19*2 and CYP2C19*3 were 68.5%,23.8%and 7.6%,respectively.The incidence of CYP2C9*3 combined with CYP2C19*2/CYP2C19*3 and CYP2C9*1*1 combined with CYP2C19*1 were 1.3%and 39.4%,respectively.The control group accounted for 60.6%and the observation group accounted for 33.2%.There were no significant differences in age,sex,hypertension,hyperlipidemia,diabetes,coronary heart disease,BMI,alcohol consumption and smoking between the two groups(P>0.05).The onset time,effective dose,average dose and INR reaching time of warfarin in observation group were significantly lower than those in control group(P<0.05).The activities of coagulation factorsⅡ,VII,IX andⅩin the observation group were significantly higher than those in the control group(P<0.05).There were significant differences in the occurrence of adverse events between the two groups(P>0.05).Anticoagulant dose of CYP2C9*1 was significantly higher than that of CYP2C9*3,anticoagulant dose of CYP2C19*1 was significantly higher than that of CYP2C19*2/CYP2C19*3,anticoagulant dose

关 键 词：CYP2C9 CYP2C19 基因多态性 非瓣膜性心房颤动 抗凝 

分 类 号：R54[医药卫生—心血管疾病]