CYP3A5、ABCB1基因多态性对中国肾移植患者服用他克莫司剂量和血药浓度的影响  

Effects of CYP3A5 and ABCB1 Gene Polymorphisms on Dosages and Blood Concentrations of Tacrolimus in Chinese Kidney Transplant Patients

作　　者：陆晓玲[1] 王雨萍 邵琨[2] 周佩军[2] 石浩强[1] 陈冰[1] LU Xiaoling;WANG Yuping;SHAO Kun;ZHOU Peijun;SHI Haoqiang;CHEN Bing(Department of Pharmacy,Rujin Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200025,China;Transplantation Center,Rujin Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200025,China)

机构地区：[1]上海交通大学医学院附属瑞金医院药剂科,上海200025 [2]上海交通大学医学院附属瑞金医院移植中心,上海200025

出　　处：《药学与临床研究》2023年第6期481-485,共5页Pharmaceutical and Clinical Research

基　　金：国家自然科学基金(81973387)。

摘　　要：目的:研究肾移植患者CYP3A5、ABCB1基因多态性对肾移植术后患者他克莫司(TAC)血药浓度及给药剂量的影响。方法:采集83例中国肾移植患者术后3个月内TAC的常规监测的谷浓度(C0)。测定受试者CYP3A5*3(rs776746)、ABCB1 1236C>T(rs1128503)、2677G>T/A(rs2032582)、3435C>T(rs1045642)位点的基因型,分析基因多态性对TAC的C0、剂量的影响。结果:患者CYP3A5、ABCB1基因型频率均符合Hardy-Weinberg平衡(P>0.05)。在移植后3个月期间,CYP3A5*3/*3型患者相较于携带*1等位基因患者,具有更高的C0和更低的剂量(P<0.05)。ABCB1 2677GG基因型的C0显著低于GT、GA、AA、TT、AT型(P<0.05);3435CT型的C0显著高于CC、TT型(P<0.05)。根据ABCB1的单倍型进行分组,并与CYP3A5进行了联合分析,结果发现,发现CYP3A5*1/*1与*1/*3组与*3/*3组中,不同ABCB1单倍型对TAC血药浓度影响的差异无统计学意义。术后随时间延长,CYP3A5*3/*3型患者的TAC剂量逐步降低,而携带*1基因患者的剂量则呈增加趋势。结论:CYP3A5比ABCB1基因多态性对肾移植受者TAC血药浓度的影响更显著,若达到相同的血药浓度,CYP3A5*3/*3型患者每日所服用的剂量更低。根据CYP3A5基因型制定给药方案,有助于尽早达到浓度标准,达到精准治疗的目标。Objective:To investigate the effects of CYP3A5 and ABCBI gene polymorphisms on blood concentrations and dosages of tacrolimus(TAC)in patients after kidney transplantation.Methods:TAC trough concentrations(Co)were collected for routine monitoring from 83 Chinese patients within 3 months after kidney transplant.Subjects were determined for their genotypes of CYP3A5*3(rs776740),ABCBI 1236C>T(rs1128503),2677G>T/A(rs2032582),3435C>T(rs1045642)loci,and of gene polymorphisms were analyzes for their effects on Co and dose of TAC.Results:The frequencies of the tested CYP3A5 and ABCB1 genotypes were consistent with the Hardy Weinberg equilibrium(P>O.05).During the three months after transplantation,patients with CYP3A5*3/*3 had higher Co and lower dose(P<0.05)compared with those carrying the*1 allele.The Co of the ABCBI 2677GG genotype was significantly lower than thsoe of the GT,GA,AA,TT and AT genotypes(P<0.05),and the Co of the 3435CT genotype was signif-icantly higher than those of the TT and CT genotypes(P<0.05).In patients with CYP3A5*1/*1,*1/*3 and*3/*3 genotypes,there was no difference among various ABCBI diplotypes.Over time after surgery,the TAC dose of the CYP3A5*3/*3 patients gradually decreased,while the dose of the patients carrying*1 al-lele showed an increasing trend.Conclusion:Compared with ABCBl,genetic polymorphism of CYP3A5 has a more significant impact on the Co of TAC in Chinese kidney transplant recipients.To reach a similar Co,patients with a CYP3A5*3/*3 genotype need a lower daily TAC dose.Dosing regimen based on the CYP3A5 genotype may be helpful in achieving target TAC concentration early,and valuable in patients re-ceiving immunosuppressive therapy after transplantation.

关 键 词：他克莫司 基因多态性 肾移植 血药浓度 CYP3A5 ABCB1 

分 类 号：R969.1[医药卫生—药理学]