膜转运体的药物遗传学：当前方法的更新。
Pharmacogenetics of membrane transporters: an update on current approaches.
机构信息
Clinical Pharmacology Program, Medical Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA.
出版信息
Mol Biotechnol. 2010 Feb;44(2):152-67. doi: 10.1007/s12033-009-9220-6.
Abstract
This review provides an overview of the pharmacogenetics of membrane transporters including selected ABC transporters (ABCB1, ABCC1, ABCC2, and ABCG2) and OATPs (OATP1B1 and OATP1B3). Membrane transporters are heavily involved in drug clearance and alters drug disposition by actively transporting substrate drugs between organs and tissues. As such, polymorphisms in the genes encoding these proteins may have significant effects on the absorption, distribution, metabolism and excretion of compounds, and may alter pharmacodynamics of many agents. This review discusses the techniques used to identify substrates and inhibitors of these proteins and subsequently to assess the effect of genetic mutation on transport, both in vitro and in vivo. A comprehensive list of substrates for the major drug transporters is included. Finally, studies linking transporter genotype with clinical outcomes are discussed.
摘要
这篇综述概述了膜转运蛋白的药物遗传学，包括选定的 ABC 转运蛋白（ABCB1、ABCC1、ABCC2 和 ABCG2）和 OATPs（OATP1B1 和 OATP1B3）。膜转运蛋白在药物清除中起着重要作用，通过在器官和组织之间主动转运底物药物来改变药物分布。因此，编码这些蛋白的基因中的多态性可能对化合物的吸收、分布、代谢和排泄有重大影响，并可能改变许多药物的药效学。本综述讨论了用于鉴定这些蛋白的底物和抑制剂的技术，并随后评估遗传突变对体外和体内转运的影响。包括了主要药物转运蛋白的底物的综合清单。最后，讨论了将转运体基因型与临床结果联系起来的研究。
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