肾移植患者术后血浆mir-627-5p表达水平与他克莫司剂量校正谷浓度相关性研究

Association of plasma mir-627-5p level with dose-adjusted trough concentration of tacrolimus in renal transplant patients

目的探讨肾移植患者术后6～10d外周血中微小RNA(microRNA)水平与他克莫司(FK506)剂量校正谷浓度之间的相关性。方法纳入109例肾移植术后进行三联免疫疗法(麦考酚酸类药物+他克莫司+泼尼松)的患者。用miRcute增强型miRNA荧光定量检测试剂盒检测microRNA表达水平,用PCRRFLP法检测CYP3A5*3基因型,同时检测FK506全血谷浓度。对肾移植患者术后6～10 d内外周血中mir-627-5p,mir-30c-1-3p,mir-378a-5p,mir-130a-3p,mir-130b表达水平与FK506剂量校正谷浓度进行相关性分析。结果在CYP3A5非表达型组患者中外周血mir-627-5p的表达水平与FK506剂量校正谷浓度呈正相关关系(Spearman相关系数=0. 311,P=0. 025)。结论肾移植外周血中mir-627水平可能是预测FK506谷浓度的生物标志物,为临床上肾移植术后FK506的剂量预测提供了新的参考因素。

Objective This study investigated the association between tacrolimus(FK506)dose-adjusted trough concentration and the microRNA expression level in plasma of renal transplant patients during the period of 6-10 d post transplantation.Methods A total of 109 post-transplant patients treated with triple immunotherapy(mycophenolic acid+tacrolimus+prednisone)were included.miRcute miRNA qPCR Detection Kit was applied for microRNA expression evaluation;and CYP3 A5*3 was genotyped via PCR-RFLP;FK506 trough blood concentration was also detected.Analysis was conducted on the association between plasma mir-627-5 p,mir-30 c-1-3 p,mir-378 a-5 p,mir-130 a-3 p and mir-130 b expression and FK506 dose-adjusted trough blood concentration.Results mir-627-5 p expression level was positively correlated to FK506 trough concentration in CYP3 A5 non-expressing patients(Spearman correlation coefficients=0.311,P=0.025).Conclusion This result proposed plasma mir-627 level in renal transplant patients as a potential biomarker for FK506 dose-adjusted trough blood concentration,providing a new reference for clinical dose prediction of FK506.