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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。
To investigate the relationship between single nucleotide polymorphism (SNP) of vitamin D receptor (VDR) and tacrolimus whole blood trough in patients with early renal transplantation after a retrospective study. A total of 114 patients were enrolled in this study. The genotypes of VDR rs2853559 and rs1540339 were detected by Agena Bioscience Mass ARRAY ~ system and CYP3A5 * 3 genotype. The tacrolimus whole blood trough concentration (C_0) on the 7th postoperative day was the data of clinical treatment monitoring (TDM). Spearman correlation analysis, Mann-Whitney U test and Kruskal-Wallis H test were used to analyze the data. The results showed that the dose-corrected trough concentration of tacrolimus of rs2853559 GA + GG genotype of VDR gene was significantly higher than that of AA genotype. After being stratified by CYP3A5 * 3 genotype, the trough concentration of VCR rs2853559 GA + GG tacrolimus was significantly higher than that of AA genotype in CYP3A5 non-expression group. Regression analysis showed that CYP3A5 * 3 and VDR rs2853559 could explain 45.6% of tacrolimus dose-corrected trough concentrations individual differences in which, among CYP3A5 non-expressive individuals, VDR rs2853559 could explain 14.4% of tacrolimus dose-corrected trough concentrations individual differences . VDR rs2853559 gene polymorphism in patients after renal transplantation correlates with tacrolimus corrected trough concentrations and this genotypic test will help guide clinical individualized use of tacrolimus.