安徽地区汉族人群CYP2C9*3和VKORC1-1639G>A基因多态性分布及对华法林稳定剂量的影响  

Distribution of CYP2C9*3 and VKORC1-1639G>A gene polymorphism in Anhui Han population and their influence on the stable dose of warfarin

作　　者：武元竹 刘俊 杨魁[1,2] 彭静 栾家杰 韦俊 张大发[3] 宋帅[4] 袁小龙[5] 王中方 张年宝 解丹 姜鹏 范洁[8] WU Yuanzhu;LIU Jun;YANG Kui;PENG Jing;LUAN Jiajie;WEI Jun;ZHANG Dafa;SONG Shuai;YUAN Xiaolong;WANG Zhongfang;ZHANG Nianbao;XIE Dan;JIANG Peng;FAN Jie(School of Pharmacy,Wannan Medical College,Wuhu 241002,Anhui,China;Department of Pharmacy,Yijishan Hospital of Wannan Medical College,Wuhu 241001,Anhui,China;Department of Cardiothoracic Surgery,Yijishan Hospital of Wannan Medical College,Wuhu 241001,Anhui,China;Department of Pharmacy,The First Affiliated Hospital of Anhui Medical University,Hefei 230022,Anhui,China;Department of Pharmacy,the Second Affiliated Hospital of Wannan Medical College,Wuhu 241000,Anhui,China;Department of Pharmacy,The People's Hospital of Xuancheng City,Xuancheng 242000,Anhui;Department of Pharmacy,Maanshan People's Hospital,Maanshan 243000,Anhui,China;Department of Pharmacy,Tongling People's Hospital,Tongling 244000,Anhui,China)

机构地区：[1]皖南医学院药学院,安徽芜湖241002 [2]皖南医学院弋矶山医院药学部,安徽芜湖241001 [3]皖南医学院弋矶山医院胸心外科,安徽芜湖241001 [4]安徽医科大学第一附属医院药剂科,安徽合肥230022 [5]皖南医学院第二附属医院药剂科,安徽芜湖241000 [6]宣城市人民医院药剂科,安徽宣城242000 [7]马鞍山市人民医院药剂科,安徽马鞍山243000 [8]铜陵市人民医院药剂科,安徽铜陵244000

出　　处：《中国临床药理学与治疗学》2022年第6期652-659,共8页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：安徽省科技攻关项目(1604a0802097);医学科研发展基金-临床与基础研究专项(YXKY-WS005E);皖南医学院重点培育项目(WK2021ZF07)。

摘　　要：目的:研究CYP2C9*3及VKORC1-1639G>A基因多态性在安徽地区汉族人群中的分布情况及对患者华法林稳定剂量的影响。方法:选取安徽省5个地区6家三级综合型医院2020年1月至2021年12月1169例患者血液样本,采用原位杂交荧光染色分析技术检测患者CYP2C9*3及VKORC1-1639G>A基因型。结果:1169例患者CYP2C9*3基因型分布情况:AA型、AC型、CC型基因频率分别为90.16%、9.24%、0.60%;VKORC1基因型分布情况:AA型、AG型、GG型基因频率分别为84.26%、14.71%、1.03%;两基因型在患者性别、年龄及地区分布上差异无统计学意义(P>0.05);755例达到华法林稳定剂量患者CYP2C9*3 AA基因型华法林日平均剂量(3.02±0.59)mg/d,显著高于AC与CC基因型患者(P<0.05);VKORC1-1639AA基因型患者华法林日平均剂量(2.72±0.40)mg/d,显著低于AG与GG基因型患者(P<0.05);达到华法林稳定剂量与未达稳定剂量患者在性别、年龄以及临床诊断上存在统计学差异(P<0.05)。结论:CYP2C9和VKORC1基因型与华法林稳定剂量有关联,以CYP2C9和VKORC1基因型为导向实施临床抗凝治疗,可为华法林个体化用药提供指导。AIM:To study the distribution of CYP2 C9*3 and VKORC1-1639 G>A gene polymorphism in Han population in Anhui province and their influence on the stable dose of warfarin.METHODS:The blood samples of 1169 patients from 6 tertiary general hospitals in 5 areas of Anhui province from January 2020 to December 2021 were selected,the genotype of CYP2 C9*3 and VKORC1-1639 G>A was detected by fluorescent staining in situ hybridization technique.RESULTS:The distribution of CYP2 C9*3 genotypes in 1169 patients:the frequencies of AA,AC and CC genes were 90.16%,9.24%and 0.60%,respectively;The distribution of VKORC1 genotype:the frequencies of AA,AG and GG genes were 84.26%,14.71%and 1.03%respectively;There was no significant difference between the two genotypes in gender,age and regional distribution(P>0.05).The average daily warfarin dose of CYP2 C9*3 AA genotype in 755 patients with stable warfarin dose was(3.02±0.59)mg/d,which was significantly higher than patients with AC genotype and CC genotype;The average daily warfarin dose of patients with VKORC1-1639 AA genotype was(2.72±0.40)mg/d,which was significantly lower than that of patients with AG genotype and GG genotype(P<0.05).And the difference was statistically significant(P<0.05);There are significant differences in gender,age and clinical diagnosis between patients with stable dose of warfarin and those without stable dose(P<0.05).CONCLUSION:CYP2 C9 and VKORC1 genotypes are associated with the stable dose of warfarin.Clinical anticoagulation therapy guided by CYP2 C9 and VKORC1 genotypes can provide guidance for individualized medication of warfarin.

关 键 词：华法林 CYP2C9*3 VKORC1-1639G>A 基因多态性 个体化用药 

分 类 号：R969[医药卫生—药理学]