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[移植治疗中的个性化医疗]

[Personalized medicine in transplantation therapy].

作者信息

Nakatani Kaname

机构信息

Department of Central Laboratory/Division of Personalized Medicine, Mie University Hospital, Tsu 514-8507, Japan.

出版信息

Rinsho Byori. 2013 May;61(5):428-33.

Abstract

Personalized medicine based on pharmacogenomics is being developed at the clinical stage. Various evidence is accumulating in transplantation therapy. Tacrolimus, a calcineurin inhibitor, is usually used for immunosuppressive therapy after transplantation. Tacrolimus is mainly metabolized by cytochrome P450 isozymes, CYP3A4 and CYP3A5, expressed in the intestine as well as in the liver. Recent studies of pharmacogenomics have reported that several single nucleotide polymorphisms (SNPs) of CYP3A5 are correlated with gene expression and enzyme activity. Phenotypes of CYP3A5 are typed as expressors (*1/*1 and *1/*3) or non-expressors (*3/*3) . In living-donor liver transplantation, CYP3A5 phenotypes could predict the blood concentration of tacrolimus. In particular, preoperative assessment of CYP3A5 genotypes in both recipients (intestine) and donors (graft liver) is required for predicting tacrolimus pharmacokinetics. In kidney transplantation, blood tacrolimus concentrations were significantly different between expressors and non-expressors. Genotyping and phenotyping of recipients were useful to predict blood tacrolimus levels in early phase of post-transplantation. Furthermore, phenotypes of CYP3A5 could predict the initial dose of tacrolimus. Combination therapy was performed after bone marrow transplantation to prevent complications. Genotyping and phenotyping of metabolic enzymes for combination dugs would be useful for predicting drug actions. In conclusion, phenotyping based on pharmacogenomics supports personalized medicine in transplantation therapy. In future, multiplex testing should be developed to support personalized medicine in various fields.

摘要

基于药物基因组学的个性化医疗正处于临床研发阶段。移植治疗领域正在积累各种相关证据。他克莫司是一种钙调神经磷酸酶抑制剂,通常用于移植后的免疫抑制治疗。他克莫司主要由细胞色素P450同工酶CYP3A4和CYP3A5代谢,这些同工酶在肠道和肝脏中均有表达。近期的药物基因组学研究报告称,CYP3A5的几个单核苷酸多态性(SNP)与基因表达及酶活性相关。CYP3A5的表型分为表达型(*1/1和1/*3)或非表达型(*3/*3)。在活体供肝移植中,CYP3A5表型可预测他克莫司的血药浓度。特别是,为了预测他克莫司的药代动力学,需要对受者(肠道)和供者(移植肝脏)的CYP3A5基因型进行术前评估。在肾移植中,表达型和非表达型患者的他克莫司血药浓度存在显著差异。对受者进行基因分型和表型分析有助于预测移植后早期的他克莫司血药水平。此外,CYP3A5表型可预测他克莫司的初始剂量。骨髓移植后采用联合治疗以预防并发症。对联合用药的代谢酶进行基因分型和表型分析有助于预测药物作用。总之,基于药物基因组学的表型分析有助于移植治疗中的个性化医疗。未来,应开展多重检测以支持各领域的个性化医疗。

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