Oetting William S, Dorr Casey, Remmel Rory P, Matas Arthur J, Israni Ajay K, Jacobson Pamala A
Department of Experimental and Clinical Pharmacology, University of Minnesota, Minneapolis, MN.
Minneapolis Medical Research Foundation, Minneapolis, MN.
Curr Transplant Rep. 2017 Jun;4(2):116-123. doi: 10.1007/s40472-017-0153-x. Epub 2017 May 24.
Identification of genetic variants to aid in individualized treatment of solid organ allograft recipients would improve graft survival. We will review the current state of knowledge for associations of variants with transplant outcomes.
Many studies have yet to exhibit robust and reproducible results, however, pharmacogenomic studies focusing on cytochrome P450 (CYP) enzymes, transporters and HLA variants have shown strong associations with outcomes and have relevance towards drugs used in transplant. Genome wide association study data for the immunosuppressant tacrolimus have identified multiple variants in the gene associated with trough concentrations. Additionally, variants had been shown to confer risk to the development of end stage renal disease in African Americans.
The field is rapidly evolving and new technology such as next generation sequencing, along with larger cohorts, will soon be commonly applied in transplantation to understand genetic association with outcomes and personalized medicine.
识别基因变异以辅助实体器官移植受者的个体化治疗，将改善移植物存活。我们将综述当前关于变异与移植结局关联的知识状态。
许多研究尚未展现出稳健且可重复的结果，然而，聚焦于细胞色素P450（CYP）酶、转运体和HLA变异的药物基因组学研究已显示出与结局有强关联，且与移植中使用的药物相关。免疫抑制剂他克莫司的全基因组关联研究数据已在与谷浓度相关的基因中识别出多个变异。此外，这些变异已被证明会使非裔美国人患终末期肾病的风险增加。
该领域正在迅速发展，诸如新一代测序等新技术，连同更大的队列，将很快普遍应用于移植领域，以了解基因与结局的关联以及个性化医疗。
