SLCO1B1基因多态性与肾移植患者他克莫司浓度相关性的研究  

Associations of SLCO1B1 polymorphisms with tacrolimus concentrations in Chinese renal transplant recipients

作　　者：刘澍[1,2] 陈荣新[3] 李军[4] 刘晓曼[2] 黄红兵[1] 傅茜[4] 王长希[4] 黄民[2] 李嘉丽[2] 

机构地区：[1]中山大学肿瘤防治中心华南肿瘤学国家重点实验室肿瘤医学协同创新中心,广东广州510060 [2]中山大学临床药理研究所,广东广州510060 [3]中山大学中山眼科中心中山大学眼科学国家重点实验室,广东广州510060 [4]中山大学附属第一医院器官移植科,广东广州510060

出　　处：《药学学报》2016年第8期1240-1244,共5页Acta Pharmaceutica Sinica

基　　金："十二五"国家科技重大专项资助项目(2012ZX09506001-004);国家自然科学基金资助项目(81102515;81320108027);广东省重点实验室建设项目(2011A060901014);广东省重大科技专项(2011A080300001)

摘　　要：考察有机阴离子转运多肽OATP1B1编码基因SLCO1B1的单核苷酸多态性（SNP）与肾移植患者术后早期他克莫司浓度之间的相关性。共纳入89例中国肾移植术后患者,采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）法对CYP3A5＊3进行基因分型,Agena Bioscience Mass ARRAYsystem对SLCO1B1 rs2306283和rs4149032进行基因分型,术后第7天他克莫司全血谷浓度为临床治疗药物监测（TDM）数据,用SPSS软件分析各基因型与他克莫司剂量校正谷浓度的相关性。结果显示,以CYP3A5＊3基因型分层后,在CYP3A5非表达型患者中,SLCO1B1 rs2306283 CC基因型组他克莫司剂量校正谷浓度显著高于CT＋TT基因型组。肾移植术后患者SLCO1B1 rs2306283基因多态性与他克莫司浓度相关,该基因型检测将有助于指导他克莫司的临床个体化用药。The study aims to investigate the associations of SLCO1B1 polymorphisms with tacrolimus concentrations in Chinese renal transplant recipients. Blood samples and clinical data were collected from 89 renal transplant recipients with tacrolimus treatment. CYP3A5＊3 genotypes were detected by PCR-RFLP method and SLCO1B1（rs2306283, rs4149032） genotypes were detected by Agena Bioscience Mass ARRAY~ system. Trough concentrations of tacrolimus on day 7 after renal transplantation were collected from clinical data. Correlations between genetic polymorphisms and tacrolimus concentrations were analyzed by SPSS. In CYP3A5 nonexpressers, the dose-adjusted concentration of tacrolimus in SLCO1B1 rs2306283 CC carriers was considerably higher than that in CT and TT carriers. The results illustrated that SLCO1B1 rs2306283 polymorphisms were associated with tacrolimus concentrations, and genotyping for this SNP may be useful for individualized medicine of tacrolimus.

关 键 词：他克莫司 SLCO1B1 单核苷酸多态性 肾移植 钙调神经蛋白抑制剂 

分 类 号：R969[医药卫生—药理学]