Multidrug resistance-associated protein 1 (MRP1/ABCC1) is the first identified member of ABCC subfamily which belongs to ATP-binding cassette (ABC) transporter superfamily.It is ubiquitously expressed in almost all human tissues and transports a wide spectrum of substrates including drugs,heavy metal anions,toxicants,and conjugates of glutathione,glucuronide and sulfate.With the advance of sequence technology,many MRP1/ABCC1 polymorphisms have been identified.Accumulating evidences show that some polymorphisms are significantly associated with drug resistance and disease susceptibility.In vitro reconstitution studies have also unveiled the mechanism for some polymorphisms.In this review,we present recent advances in understanding the role and mechanism of MRP1/ABCC1 polymorphisms in drug resistance,toxicity,disease susceptibility and severity,prognosis prediction,and methods to select and predict functional polymorphisms.%ABCC亚家族属于ABC转运体超家族,ABCC1是ABCC亚家族第一个被发现的成员.它分布于体内几乎所有组织,可以转运多种不同底物,包括药物、重金属离子、机体代谢毒物、谷胱甘肽、葡糖醛酸和硫结合物.随着测序技术的发展,近年来发现很多ABCC1基因多态.越来越多的证据表明一些多态与药物耐药和疾病易感性密切相关.同时,一些体外重构突变的方法也揭示了部分多态的作用机制.总结ABCC1基因多态的最新研究进展(包括ABCC1多态与药物耐药,药物毒性,疾病易感性和严重性,疾病预后的关系,它们的作用机制及如何选择和预测功能性多态)具有重要的意义.
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