VDR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 VDR polymorphisms with tacrolimus concentrations in Chinese renal transplant recipients

作　　者：覃利[1] 李嘉丽[1] 刘晓曼[1] 陈徐涛 刘澍[3] 刘龙山[2] 王长希[2] 黄民[1] 

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]中山大学附属第一医院器官移植科,广东广州510080 [3]中山大学肿瘤防治中心药学部,广东广州510080

出　　处：《药学学报》2017年第5期760-765,共6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);国家重点研发计划项目(2016YFC0905000);广东省重点实验室建设项目(2011A060901014);广东省重大科技专项(2011A080300001;2012A080202013)

摘　　要：通过回顾性研究,探讨维生素D受体(VDR)的单核苷酸多态性(SNP)与肾移植术后早期患者体内他克莫司全血谷浓度的相关性。共纳入114例活体肾移植术后服用他克莫司+霉酚酸酯+糖皮质激素的患者,采用Agena Bioscience Mass ARRAY~ system检测VDR rs2853559和rs1540339基因型,采用PCR-RFLP法检测CYP3A5*3基因型,术后第7天他克莫司全血谷浓度(C_0)为临床治疗药物监测(TDM)数据,采用Spearman相关分析、Mann-Whitney U检验、Kruskal-Wallis H检验进行数据分析。结果显示,VDR基因rs2853559 GA+GG型他克莫司剂量校正谷浓度显著高于AA型。以CYP3A5*3基因型进行分层后,在CYP3A5非表达型组中VDR rs2853559 GA+GG型他克莫司剂量校正谷浓度显著高于AA型。回归分析表明,CYP3A5*3及VDR rs2853559能解释45.6%的他克莫司剂量校正谷浓度个体差异,在CYP3A5非表达者中,VDR rs2853559能解释14.4%的他克莫司剂量校正谷浓度个体差异。肾移植术后患者VDR rs2853559基因多态性与他克莫司校正谷浓度相关,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 paper was aimed to investigate the association of VDR polymorphisms with tacrolimus （FK506） concentration in Chinese renal transplant recipients. A total of 114 renal transplant recipients receiving tacrolimus were genotyped for VDR rs1540339 and rs2853559 by Agena Bioscience MassARRAY system and CYP3A5＊3 by PCR-RFLP method. Trough concentrations of tacrolimus on day 7 after renal transplantation were collected from clinical data. Statistical analysis was performed with Spearman＇s correlation, Mann- Whitney U test and Kruskal-Wallis H test. The dose-adjusted concentration of tacrolimus in VDR rs2853559 GA and GG carriers were considerably higher than that of AA carriers. After stratification by CYP3AS＊3 genotypes, VDR rs2853559 GA and GG carriers had a higher dose-adjusted tacrolimus concentration than that in AA carriers in CYP3A5 nonexpresser. CYP3AS＊3 and VDR rs2853559 explained 45.6% variability oftacrolimus Co/D. In CYP3A5 non-expressers, VDR rs2853559 explained 14.4% variability of tacrolimus Co/D. The results illustrated that VDR rs2853559 polymorphisms was associated with tacrolimus concentrations, and the determination of this SNP may be useful for individualized medicine of tacrolimus.

关 键 词：他克莫司 VDR 基因多态性 肾移植 

分 类 号：R969[医药卫生—药理学]