转运体基因多态性与霉酚酸类药物暴露和不良反应相关性的研究进展

Association between transporter gene polymorphism and mycophenolic acids exposure and related adverse reactions

霉酚酸(MPA)类药物是一类广泛应用于器官移植免疫排斥反应预防和自身免疫性疾病治疗的脱氧核糖(或核糖)核酸合成抑制剂,其治疗窗窄,呈非线性药代动力学特征,个体差异显著,具有明显且重要的肠肝循环过程。基因多态性是MPA代谢差异的重要影响因素之一。MPA肠肝循环涉及多种转运体,因此,除代谢酶外,相关转运体基因多态性也与MPA代谢紧密相关。目前转运体基因多态性与MPA暴露和不良反应的相关性研究逐渐成为新的热点。本文旨在综述转运体基因(ABCB1、ABCC2、ABCG2、SLCO1B1和SLCO1B3)多态性对MPA体内暴露和相关不良反应的影响,为MPA个体化用药和减少不良反应提供参考。

Mycophenolic acids(MPA),a class of inhibitors of deoxyribonucleic acid or ribonucleic acid synthesis,have been widely used in the prevention of allograft rejection after organ transplantation and the treatment of autoimmune diseases.MPA was found to have a narrow therapeutic window,nonlinear pharmacokinetic characteristics,strong individual difference and a distinct and vital enterohepatic circulation.Gene polymorphism is an important factor in MPA metabolism.MPA enterohepatic circulation involves many transporters.In addition to metabolic enzymes,gene polymorphism of transporters was also closely associated with MPA metabolism.Currently,the association of transporters gene polymorphism and MPA exposure and its adverse reactions became a new hotspot.We reviewed the effects of transporter genes(ABCB1,ABCC2,ABCG2,SLCO1B1,and SLCO1B3)polymorphism on MPA exposure and related adverse reactions,to provide reference for individualized administration of MPA and reduction of adverse reactions.