VDR基因多态性与肾移植患者他克莫司浓度相关性的研究

发布时间：2018-03-30 17:42

本文选题：他克莫司　切入点：VDR　出处：《药学学报》2017年05期

【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~汶 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。
[Abstract]:A retrospective study was conducted to investigate the association of single nucleotide polymorphisms (SNPs) of vitamin D receptor (VDR) with the whole blood valley concentration of tacrolimus in the early stage of renal transplantation.The genotypes of VDR rs2853559 and rs1540339 were detected by Agena Bioscience Mass arrayven system and CYP3A5*3 genotypes were detected by PCR-RFLP method in 114 patients who were treated with tacrolimolic acid glucocorticoid after renal transplantation in vivo.On the 7th day after operation, tacrolimus whole blood valley concentration (C0) was used as clinical drug monitoring data. Spearman correlation analysis was used to analyze the data by Kruskal-Wallis H test with Mann-Whitney U test.The results showed that rs2853559 GA GG dosimetric correction valley concentration of VDR gene was significantly higher than that of AA type.After stratification with CYP3A5*3 genotype, the dosimetric correction valley concentration of VDR rs2853559 GA GG type tacrolimus was significantly higher than that of AA type in CYP3A5 non-expression group.The regression analysis showed that CYP3A5H3 and VDR rs2853559 could explain 45.6% of the individual differences in dosimetric corrected valley concentration of tacrolimus, and 14.4% of the nonexpressed CYP3A5 could explain the individual difference of tacrolimus dosimetric corrected valley concentration.The polymorphism of VDR rs2853559 gene is associated with tacrolimus corrected valley concentration in renal transplantation patients. This genotype detection will be helpful to guide tacrolimus in clinical individualized drug use.
【作者单位】：中山大学药学院临床药理研究所;中山大学附属第一医院器官移植科;中山大学肿瘤防治中心药学部;
【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)
【分类号】：R692

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