Salvadori Maurizio, Tsalouchos Aris
Department of Renal Transplantation, Careggi University Hospital, Florence 50139, Italy.
Nephrology and Dialysis Unit, Saints Cosmas and Damian Hospital, Pescia 51017, Italy.
World J Transplant. 2020 May 29;10(5):90-103. doi: 10.5500/wjt.v10.i5.90.
In recent years, pharmacogenetics has emerged as an important tool for choosing the right immunosuppressant drug and its appropriate dose. Indeed, pharmacogenetics may exert its action on immunosuppressant drugs at three levels. Pharmacogenetics identifies and studies the genes involved in encoding the proteins involved in drug pharmacokinetics and in encoding the enzymes involved in drug degradation. Pharmacogenetics is also relevant in encoding the enzymes and proteins involved in codifying the transmembrane proteins involved in transmembrane passage favoring the absorption and intracellular action of several immunosuppressants. Pharmacogenetics concern the variability of genes encoding the proteins involved as immunosuppressant triggers in the pharmacodynamic pathways. Of course, not all genes have been discovered and studied, but some of them have been clearly examined and their relevance together with other factors such as age and race has been defined. Other genes on the basis of relevant studies have been proposed as good candidates for future studies. Unfortunately, to date, clear conclusions may be drawn only for those drugs that are metabolized by CYP3A5 and its genotyping before kidney, heart and lung transplantation is recommended. The conclusions of the studies on the recommended candidate genes, together with the development of omics techniques could in the future allow us to choose the right dose of the right immunosuppressant for the right patient.
近年来，药物遗传学已成为选择合适的免疫抑制剂药物及其适当剂量的重要工具。事实上，药物遗传学可能在三个层面上对免疫抑制剂药物发挥作用。药物遗传学识别并研究参与编码药物药代动力学相关蛋白质以及参与药物降解的酶的基因。药物遗传学在编码参与几种免疫抑制剂跨膜转运、促进其吸收和细胞内作用的跨膜蛋白的酶和蛋白质方面也具有相关性。药物遗传学涉及编码作为药效学途径中免疫抑制剂触发因素的相关蛋白质的基因的变异性。当然，并非所有基因都已被发现和研究，但其中一些已得到明确研究，并且它们与年龄和种族等其他因素的相关性也已明确。基于相关研究，其他基因也被提议作为未来研究的良好候选对象。不幸的是，迄今为止，仅对于那些由CYP3A5代谢的药物可以得出明确结论，并且建议在肾、心和肺移植前进行其基因分型。关于推荐候选基因的研究结论，连同组学技术的发展，未来可能使我们能够为合适的患者选择合适的免疫抑制剂的合适剂量。
