对儿童异基因造血干细胞移植患者环孢素浓度的影响因素分析  

Analysis of factors influencing cyclosporine concentration in pediatric allogeneic hematopoietic stem cell transplant recipients

作　　者：王翔桂 莫小兰 江华[3] 刘莎[3] 李焱[4] 林玉贤 郑伟[2] 黄琼波 陈霆锋 黄民[1] 李嘉丽[1] WANG Xiang-gui;MO Xiao-lan;JIANG Hua;LIU Sha;LI Yan;LIN Yu-xian;ZHENG Wei;HUANG Qiong-bo;CHEN Ting-feng;HUANG Min;LI Jia-li(Institute of Clinical Pharmacology,School of Pharmaceutical Sciences,Sun Yai-Sen University,Guangzhou 510080,Guangdong Province,China;Department of Pharmacy,Guangzhou Medical University,Guangzhou 510623,Guangdong Province,China;Department of Hematology/Oncology,Guangzhou Medical University,Guangzhou 510623,Guangdong Province,China;Guangzhou Cord Blood Bank,Guangzhou Women and Children's Medical Center,Guangzhou Medical University,Guangzhou 510623,Guangdong Province,China;Department of Pharmacy,The Fifth Affiliated Hospital of Guangzhou Medical University,Guangzhou 510700,Guangdong Province,China)

机构地区：[1]中山大学药学院临床药理研究所,广东广州510080 [2]广州医科大学附属广州市妇女儿童医疗中心药学部,广东广州510623 [3]广州医科大学附属广州市妇女儿童医疗中心血液肿瘤科,广东广州510623 [4]广州医科大学附属广州市妇女儿童医疗中心脐血库,广东广州510623 [5]广州医科大学附属第五医院药学部,广东广州510700

出　　处：《中国临床药理学杂志》2022年第13期1435-1439,共5页The Chinese Journal of Clinical Pharmacology

基　　金：广东省自然科学基金资助项目(2021A1515011308);广州市科技局市校联合基金资助项目(202102010237)。

摘　　要：目的探讨儿童异基因造血干细胞移植患者移植早期环孢素剂量校正谷浓度与临床特征及CYP3A4/5和ABCB1的基因多态性的相关性。方法回顾性收集接受异基因造血干细胞移植并使用环孢素预防移植物抗宿主病的儿童患者,采集患者的临床特征,使用Agena Bioscience MassARRAYsystem检测患者ABCB1(rs1045642、rs3842和rs1128503)、CYP3A4(rs2242480)和CYP3A5(rs776746)的基因型。采用Mann-Whitney U检验方法分析性别、原发病、合用唑类药物及CYP3A5的基因型与环孢素A(CsA)剂量校正谷浓度(C/D)的相关性,采用Kruskal-Wallis H检验方法ABCB1和CYP3A4的基因型与CsA C/D的相关性,采用Spearman相关方法分析其他临床特征与CsA C/D的相关性。结果ABCB1(rs1045642、rs3842和rs1128503)、CYP3A4(rs2242480)和CYP3A45(rs776746)的基因多态性均与CsA C/D无关;红细胞比容与CsA C/D呈正相关(r=0.39,P<0.05)。结论CYP3A4/5和ABCB1的基因多态性与患者CsA C/D无关,红细胞比容显著影响患者CsA C/D,需密切关注患者的红细胞比容,并及时调整CsA的剂量。此研究为指导儿童患者CsA的个体化用药提供了参考。Objective To evaluate the effects of clinical features and genetic polymorphisms of CYP3A4/5 and ABCB1 on dose-adjusted trough concentration of cyclosporine in pediatric allogeneic hematopoietic stem cell transplant recipients. Methods The pediatric patients who received allogeneic hematopoietic stem cell transplantation and used cyclosporine to prevent graft-versus-host disease were included, and the clinical characteristics of the patients were collected. Agena Bioscience MassARRAYsystem was used to analyze genotypes of ABCB1(rs1045642, rs3842, and rs1128503), CYP3A4(rs2242480) and CYP3A5(rs776746). Mann-Whitney U test was used to analyze the correlation between sex, primary disease, combined use of azoles and CYP3A5 genotypes and cyclosporin A(CsA) dose/weight-adjusted trough concentration(C/D), Kruskal-Wallis H test was used to analyze the correlation between ABCB1 and CYP3A4 genotypes and CsA C/D, and the correlation between other clinical features and CsA C/D was analyzed by Spearman correlation method. Results The genetic polymorphisms of ABCB1( rs1045642,rs3842,and rs1128503),CYP3A4( rs2242480) and CYP3A5( rs776746)were not associated with CsA C/D,and hematocrit was positively correlated with CsA C/D( r = 0. 39,P < 0. 05).Conclusion There was no correlation between genetic polymorphisms of CYP3A4/5,ABCB1 and CsA C/D,and hematocrit significantly affects CsA C/D. Therefore,it is necessary to monitor the patient’s hematocrit and adjust the dose of CsA. This study provides a reference for personalized medicine of CsA in children.

关 键 词：环孢素 基因多态性 血药浓度 造血干细胞移植 儿童 

分 类 号：R97[医药卫生—药品]