Genetics of acute rejection after kidney transplantation.
Genetics of acute rejection after kidney transplantation.
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DOI：
10.1111/tri.13084
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发表时间：
2018-03
期刊：
影响因子：
--
通讯作者：
Israni AK
中科院分区：
文献类型：
--
作者：
Dorr CR;Oetting WS;Jacobson PA;Israni AK
近年来，肾移植后急性排斥反应（AR）的治疗有所改善，但成功的结局仍有局限性。这篇综述文章涵盖了关于AR肾和继发性肝同种异体移植的受体和供体遗传学的文献。肾移植中AR的候选基因和全基因组关联研究（GWASs）已被广泛开展。肾脏和肝脏中AR的遗传相关性大多较弱，并且在大多数情况下，这种相关性不可重现。AR研究的局限性是缺乏足够大的人群，这些人群可以解释研究AR表型的人群分层，在这个时代，AR表型发生在<10%的移植中。此外，AR表型很难定义，分类的定义随着时间的推移而演变。与他克莫司药物基因组学相关的文献是稳健的，并已在许多研究中得到验证。基因表达和AR之间的关联正在成为结果和AR分类的标志物。在未来，移植前基因型的AR风险预测，基于基因型的免疫抑制剂给药，和药物基因组学标记选择AR维持或治疗和表达标记活检的组合可能提供有价值的临床工具，指导治疗。
Treatment of acute rejection (AR) following kidney transplantation has improved in recent years, but there are still limitations to successful outcomes. This review article covers literature in regard to recipient and donor genetics of AR kidney and secondarily of liver allografts. Many candidate gene and some genome-wide association studies (GWASs) have been conducted for AR in kidney transplantation. Genetic associations with AR in kidney and liver are mostly weak, and in most cases, the associations have not been reproducible. A limitation in the study of AR is the lack of sufficiently large populations that account for population stratification to study the AR phenotype which in this era occurs in <10% of transplants. Furthermore, the AR phenotype has been difficult to define and the definitions of classifications have evolved over time. Literature related to the pharmacogenomics of tacrolimus is robust and has been validated in many studies. Associations between gene expression and AR are emerging as markers of outcomes and AR classification. In the future, combinations of pretransplant genotype for AR risk prediction, genotype-based immune suppressant dosing, and pharmacogenomic markers to select AR maintenance or treatment and expression markers from biopsies may provide valuable clinical tools for guiding treatment.
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