次黄苷三磷酸焦磷酸酶遗传多态性对硫嘌呤类药物疗效和不良反应影响的研究进展

摘要/Abstract

摘要： 硫嘌呤类药物作为一类常用的免疫抑制剂,广泛应用于临床。然而其治疗窗窄,药动学个体差异大一直是困扰该类药物临床应用的难题。尽管硫嘌呤甲基转移酶(thiopurine methyltransferase,TPMT)基因多态性被认为是影响硫嘌呤类药物药动学的主要遗传因素,但研究结论并不统一。而最近的一些研究将焦点集中到了次黄苷三磷酸焦磷酸酶(inosine triphosphate pyrophosphatase,ITPA)的遗传多态性上。因此,本文就ITPA遗传多态性对硫嘌呤类药物疗效和毒性影响的研究进展作一综述,以期为临床个体化应用硫嘌呤类药物提供理论指导。

关键词: 硫嘌呤类药物, 基因多态性, 次黄苷三磷酸焦磷酸酶, 个体差异

Abstract: Thiopurines, one kind of immunosuppressive agents,represent an effective and widely prescribed therapy in clinical application. However, the narrow therapeutic window and pharmacokinetic variability has been always a difficult problem to the clinical use of these drugs. Although the gene polymorphisms of thiopurine methyltransferase (TPMT) are considered to be the main genetic factors that affect pharmacokinetics of thiopurine drugs, but the conclusions of these studies are not consistent. However, some recent studies have focused on the genetic polymorphisms of inosine triphosphate pyrophosphatase (ITPA). Therefore, this review summarizes the recent research progress on influence of the genetic polymorphisms of ITPA on efficacy and toxicity of thiopurines, so as to provide guidance for individualized treatment in the clinical practice.

Key words: thiopurines, genetic polymorphism, inosine triphosphate pyrophosphatase, individual variation

中图分类号:

R968

冯静, 吴玥, 戎佩佩, 沈秉正, 周丁山, 施偲, 宋金春. 次黄苷三磷酸焦磷酸酶遗传多态性对硫嘌呤类药物疗效和不良反应影响的研究进展[J]. 中国临床药理学与治疗学, 2014, 19(12): 1435-1440.

FENG Jing, WU Yue, RONG Pei-pei, SHEN Bing-zheng, ZHOU Ding-shan, SHI Cai, SONG Jin-chun. Progress on effects of pharmacogenetics of inosine triphosphate pyrophosphatase on improving the individualized thiopurine therapy[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2014, 19(12): 1435-1440.

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