Research Division of Clinical Pharmacology, First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
Department of Urology, First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
Curr Drug Metab. 2018;19(14):1199-1205. doi: 10.2174/1389200219666171227201608.
Mycophenolic Acid (MPA) is an immunosuppressive drug widely used in the treatment of organ transplantation and autoimmune diseases. Pharmacokinetics and pharmacodynamics of MPA varies between individuals, the potential reasons being the genetic polymorphisms in key enzymes, drug transporters and target proteins of MPA.
We try to provide pharmacogenomics information for drug selection and dose adjustment, aiming to improve drug efficacy and reduce side effects in clinical application of MPA.
In this review, we summarize the literatures in Pubmed that reported MPA-related Single Nucleotide Polymorphisms (SNPs) of renal transplant patients in recent 15 years.
Genetic polymorphisms involving uridine diphosphate glucuronosyltransferase enzymes, organic anion transport polypeptides, multidrug resistance-associated protein 2, inosine monophosphate dehydrogenase and immune- response mediators may be associated with the metabolism, efficacy and toxicity of MPA, thus resulting in different MPA exposure and patient outcomes in renal transplantation.
Several SNPs show significant association with MPA pharmacokinetics and pharmacodynamics, but conflicting results are reported, and no studies on MPA genetic polymorphisms have been translated into clinical practice. More prospective studies are needed to clear the role of genetic polymorphisms on MPA in renal transplantation patients.
霉酚酸（MPA）是一种广泛用于器官移植和自身免疫性疾病治疗的免疫抑制剂。MPA 的药代动力学和药效学在个体之间存在差异，潜在的原因是 MPA 的关键酶、药物转运体和靶蛋白的遗传多态性。
我们试图为药物选择和剂量调整提供药物遗传学信息，旨在提高 MPA 临床应用的疗效并降低副作用。
在这篇综述中，我们总结了近 15 年来 Pubmed 报道的与肾移植患者 MPA 相关的单核苷酸多态性（SNP）的文献。
涉及尿苷二磷酸葡萄糖醛酸转移酶、有机阴离子转运多肽、多药耐药相关蛋白 2、肌苷单磷酸脱氢酶和免疫反应调节剂的遗传多态性可能与 MPA 的代谢、疗效和毒性有关，从而导致肾移植患者的 MPA 暴露和患者结局不同。
有几个 SNP 与 MPA 的药代动力学和药效学有显著相关性，但报道的结果存在冲突，且 MPA 遗传多态性的研究尚未转化为临床实践。需要更多的前瞻性研究来阐明遗传多态性对肾移植患者 MPA 的作用。
