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移植后糖尿病的药物遗传学

Pharmacogenetics of posttransplant diabetes mellitus.

作者信息

Lancia P, Adam de Beaumais T, Jacqz-Aigrain E

机构信息

Department of Pediatric Pharmacology and Pharmacogenetics, Robert Debré Hospital, APHP, Paris, France.

Paris Diderot Sorbonne Paris Cité, University of Paris Diderot Sorbonne, Paris Cité, Paris, France.

出版信息

Pharmacogenomics J. 2017 Jun;17(3):209-221. doi: 10.1038/tpj.2017.1. Epub 2017 Mar 28.

Abstract

Many factors (physiological, pathological, environmental or genetic) are associated with variability in drug effect. Most patients respond to a standard treatment but the drug may be ineffective or toxic. In this review, we focused on genetic markers of posttransplant diabetes mellitus (PTDM) after renal transplantation, a frequent complication of immunosuppressive therapy and important risk factor of graft loss and mortality. An initial literature search identified 100 publications and among them 32 association studies were retrieved under 'Pharmacogenetics and PTDM'. Thirty-five variants in 25 genes with an impact on insulin secretion, disposition or effect were significantly associated with PTDM. The population studied, immunosuppressive regimen, follow-up, PTDM diagnostic and genetic variations tested were highly variable between studies. Although pharmacogenetic biomarkers are key tools of great promise for preventing toxicities and improving event-free survival rates, replication studies are required to select validated biomarkers linked to the occurrence of PTDM and select appropriate immusuppressive treatment to improve renal graft and patient outcome.

摘要

许多因素(生理、病理、环境或遗传)与药物效应的变异性相关。大多数患者对标准治疗有反应,但药物可能无效或有毒。在本综述中,我们重点关注肾移植后移植后糖尿病(PTDM)的遗传标志物,这是免疫抑制治疗的常见并发症,也是移植物丢失和死亡的重要危险因素。初步文献检索确定了100篇出版物,其中32项关联研究在“药物遗传学与PTDM”下被检索到。25个基因中的35个变异对胰岛素分泌、处置或效应有影响,与PTDM显著相关。各研究之间所研究的人群、免疫抑制方案、随访、PTDM诊断和检测的基因变异差异很大。尽管药物遗传学生物标志物是预防毒性和提高无事件生存率的极有前景的关键工具,但仍需要进行重复研究,以选择与PTDM发生相关的经过验证的生物标志物,并选择合适的免疫抑制治疗方案,以改善肾移植和患者的预后。

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