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器官移植的临床药物基因组学更新。

Update on the clinical pharmacogenomics of organ transplantation.

机构信息

Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, 10903 New Hampshire Avenue, Building 51, Room 3184, Silver Spring, MD 20993, USA.

出版信息

Pharmacogenomics. 2010 Feb;11(2):227-36. doi: 10.2217/pgs.09.177.

Abstract

Organ transplantation suffers from a static graft and patient survival rate, and a high incidence of serious adverse drug effects. The pharmacogenomics of organ transplantation has emerged only recently and is complementary to the immunogenetic information that has accumulated over the past decade. Gene polymorphism studies have focused on the genes that interact across the group of immunosuppressants, including ciclosporin, tacrolimus, sirolimus and corticosteroids. The polymorphisms that hold the most potential for use in a drug selection algorithm are in genes CYP3A5, ABCB1, IMPDH1 and IMPDH2, and cytokines and growth factors. Gene-expression arrays have led to gene-expression testing, such as the use of AlloMap((R)) with heart transplant patients. The expanded use of gene-expression assays, proteomics and drug selection algorithms in organ transplantation will progress slowly and may be outpaced by drug test co-development programs for new transplant drugs. In the future, clinical pharmacogenomics will be a routine part of patient care for organ transplant patients.

摘要

器官移植存在移植物和患者存活率的静态问题,且严重药物不良反应发生率较高。器官移植的药物基因组学最近才出现,与过去十年积累的免疫遗传学信息互补。基因多态性研究集中在相互作用的免疫抑制剂群中的基因,包括环孢素、他克莫司、西罗莫司和皮质类固醇。在药物选择算法中最具应用潜力的多态性存在于 CYP3A5、ABCB1、IMPDH1 和 IMPDH2 基因以及细胞因子和生长因子中。基因表达谱导致了基因表达测试,例如在心脏移植患者中使用 AlloMap((R))。基因表达检测、蛋白质组学和药物选择算法在器官移植中的广泛应用将进展缓慢,可能落后于新移植药物的药物测试联合开发计划。在未来,临床药物基因组学将成为器官移植患者患者护理的常规部分。

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