Pallio Giovanni, Irrera Natasha, Bitto Alessandra, Mannino Federica, Minutoli Letteria, Rottura Michelangelo, Pallio Socrate, Altavilla Domenica, Alibrandi Angela, Marciano Maria Concetta, Righi Maria, Mannucci Carmen, Arcoraci Vincenzo, Squadrito Francesco
Department of Clinical and Experimental Medicine, University of Messina, Via C. Valeria, 98125 Messina, Italy.
Department of Biomedical, Dental, Morphological and Functional Imaging Sciences, University of Messina, Via C. Valeria, 98125 Messina, Italy.
J Pers Med. 2020 Jun 1;10(2):47. doi: 10.3390/jpm10020047.
Precise tacrolimus treatment in transplanted patients is achieved in the clinical setting by performing therapeutic drug monitoring (TDM) and consequently adjusting therapy. The aim of this study was to retrospectively analyze the variability in tacrolimus blood levels throughout 2 years of observation in 75 transplanted patients and to investigate if tacrolimus blood levels correlate with presence of genetic polymorphisms, thus modifying tacrolimus pharmacokinetics. CYP3A51 (G6986A), CYP3A41B (A392G), CYP3A4*22, ABCB1 (C3435T; C1236T; G2677A/T), SLCO1B1 (T521C), polymorphisms were analyzed. Based on the effect of their genotypes, patients were stratified into 5 groups: (1) reduced tacrolimus metabolism (RM), (2) increased metabolism (IM), (3) transporters polymorphisms (TM), (4) metabolism and transporter polymorphisms (AM) and (5) no mutations (Wild Type, WT). The percentage of the samples out of therapeutic range was significantly higher in the IM group than in the WT group ( = 0.001), as well as compared to the TM group ( = 0.004). Only IM pattern ( = 0.015) resulted as an independent predictor of number of tacrolimus blood levels out of therapeutic range. RM pattern ( = 0.006) was inversely related to the administered dose. Therefore, genotyping could become a standard practice before tacrolimus prescription thus decreasing side effects, increasing efficacy and reducing the economic burden for the national health system.
在临床环境中，通过进行治疗药物监测（TDM）并相应调整治疗方案，可实现对移植患者的他克莫司精准治疗。本研究的目的是回顾性分析75例移植患者在2年观察期内他克莫司血药浓度的变异性，并研究他克莫司血药浓度是否与基因多态性的存在相关，从而改变他克莫司的药代动力学。分析了CYP3A51（G6986A）、CYP3A41B（A392G）、CYP3A4*22、ABCB1（C3435T；C1236T；G2677A/T）、SLCO1B1（T521C）等基因多态性。根据患者基因型的影响，将患者分为5组：（1）他克莫司代谢降低（RM）组，（2）代谢增加（IM）组，（3）转运体多态性（TM）组，（4）代谢和转运体多态性（AM）组，（5）无突变（野生型，WT）组。IM组超出治疗范围的样本百分比显著高于WT组（P = 0.001），与TM组相比也更高（P = 0.004）。只有IM模式（P = 0.015）是他克莫司血药浓度超出治疗范围数量的独立预测因素。RM模式（P = 0.006）与给药剂量呈负相关。因此，基因分型可在他克莫司处方前成为标准做法，从而减少副作用、提高疗效并减轻国家卫生系统的经济负担。
