CYP3A5基因多态性与肝移植术后早期他克莫司浓度/剂量比的关系  

Correlation Between CYP3A5 Gene Polymorphism and Tacrolimus Concentration/Dose Ratio in the Early Postoperative Period After Liver Transplantation

作　　者：王新 王华光[3] 邱葵[3] 艾超[2] 刘丽宏 WANG Xin;WANG Huaguang;QIU Kui;AI Chao;LIU Lihong(School of Pharmaceutical Sciences,Capital Medical University,Beijing 100069,China;Dept.of Pharmacy,Beijing Tsinghua Changgung Hospital,School of Clinical Medicine,Tsinghua University,Beijing 102218,China;Dept.of Pharmacy,Beijing Chaoyang Hospital,Capital Medical University,Beijing 100020,China;Dept.of Pharmacy,China-Japan Friendship Hospital,Beijing 100029,China)

机构地区：[1]首都医科大学药学院,北京100069 [2]清华大学附属北京清华长庚医院药学部/清华大学临床医学院,北京102218 [3]首都医科大学附属北京朝阳医院药事部,北京100020 [4]中日友好医院药学部,北京100029

出　　处：《中国医院用药评价与分析》2022年第1期55-58,共4页Evaluation and Analysis of Drug-use in Hospitals of China

摘　　要：目的:探讨供受体CYP3A5基因多态性对肝移植术后早期他克莫司浓度/剂量比(C/D)的影响。方法:回顾性收集2020年在清华大学附属北京清华长庚医院首次接受肝移植的患者71例,记录其术后2周、3周和4周时服用的他克莫司剂量及相应时间点的血药浓度(C),得到每千克日剂量(D),分别计算C/D。采用荧光原位杂交技术测定供受体CYP3A5的基因型,根据基因型进行分组,将CYP3A5*1/*1和CYP3A5*1/*3归为表达组,将CYP3A5*3/*3归为非表达组,分别分析并联合分析供受体基因型对于C/D的影响,同时联合分析供受体基因型对于肝移植术后肝功能恢复正常率的影响。结果:术后2周、3周和4周时,供体和受体表达组的他克莫司C/D均低于非表达组,差异有统计学意义(P<0.05)。供受体联合分析结果显示,供体非表达/受体非表达组的他克莫司C/D高于供体表达/受体表达组、供体表达/受体非表达组和供体非表达/受体表达组,差异均有统计学意义(P<0.05)。术后1个月内,供体表达/受体表达组、供体表达/受体非表达组、供体非表达/受体表达组和供体非表达/受体非表达组组间肝功能恢复正常率比较,差异无统计学意义(P>0.05)。结论:供受体CYP3A5基因多态性均是影响肝移植术后患者他克莫司C/D的遗传因素,携带CYP3A5*3/*3基因型的患者,在达到相同目标的血药浓度时可能需要更低的剂量,用药前进行基因型检测能够更有效地指导他克莫司的临床应用。OBJECTIVE:To investigate the effect of donor-recipient CYP3A5 gene polymorphisms on the tacrolimus concentration/dose ratio(C/D)in the early postoperative period after liver transplantation.METHODS:Seventy-one patients who received liver transplantation for the first time at Beijing Tsinghua Changgung Hospital,School of Clinical Medicine,Tsinghua University in 2020 were retrospectively collected.Tacrolimus dose at 2,3 and 4 weeks after surgery and blood concentration(C)at corresponding time points were recorded to obtain daily dose per kilogram(D),and C/D value was calculated respectively.The genotypes of donor-recipient CYP3A5 were determined by fluorescence in situ hybridization,and CYP3A5*1/*1 and CYP3A5*1/*3 were grouped according to genotype,and CYP3A5*3/*3 were grouped as the expression group and CYP3A5*3/*3 were grouped as the non-expression group,the effects of donor-recipient genotype on C/D value were analyzed separately and jointly,meanwhile,the donor-recipient genotypes were analyzed to compare the normal recovery rate of liver function after liver transplantation.RESULTS:At 2,3 and 4 weeks after surgery,C/D values were lower in both donor and recipient expressing group than in the non-expressing group,with statistically significant differences(P<0.05).C/D values of donor non-expression/receptor non-expression group were higher than those of donor expression/receptor expression group,donor expression/receptor non-expression group and donor non-expression/receptor expression group,the difference was statistically significant(P<0.05).At 1 month after surgery,there was no significant difference in the normal rate of liver function between donor expression/receptor expression group,donor expression/receptor non-expression group,donor non-expression/receptor expression group and donor non-expression/receptor non-expression group(P>0.05).CONCLUSIONS:Both donor-recipient CYP3A5 gene polymorphisms are genetic factors affecting tacrolimus C/D in patients after liver transplantation.Patients carrying CYP3A5*3/*

关 键 词：肝移植 CYP3A5 他克莫司 基因多态性 浓度/剂量比 

分 类 号：R979.5[医药卫生—药品]