ABCC1基因多态性从发现到临床应用.pdf

中南大学学报(医学版)
J Cent South Uniu (Med Sci
2011,36(10)htp://www.csumedorghttp://xbyx.xysm,net
Multidrug resistance-associated protein 1
(MRP1/ABCCI )polymorphism: from
discovery to clinical application
YIN Jiye", ZHANG Jianting
(1. Department of Pharmacology/Toxicology; 2.IU Simon Cancer Center, Indiana
University School of Medicine, Indianapolis Indiana 46202, USA)
Abstract: Multidrug resistance-associated protein 1(MRP//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
including drugs, heavy metal anions, toxicants, and conjugates of glutathione, glucuronide and sul
fate. With the advance of sequence technology, many MRP1/ABCC/ polymorphisms have been i
dentified. 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 MRP]/ABCC:I polymorphisms in drug resistance, toxicity, disease sus
ceptibility and severity, prognosis prediction and methods to select and predict functional polymor
Key words: multidrug resistance-associated protein 1; ABCC1; single nucleotide poly-
morphism; drug resistance; prognosis; disease susceptibilit
MRPI/ABCC1基因多态性:从发现到临床应用
尹继业…,张建亭2
(印第安纳大学医学院1.药理与毒理学系;2. Simon舯瘡研究中心,
印第安纳州印第安纳波利斯46202,美国)
[摘要]ABCC亚家族属于ABC转运体超家族, ABCCI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、黼醬醛酸和
硫结合物。随着测序技术的发展,近年来发现很多ABCC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ABCC7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。
[关键词]多药耐药相关蛋白1;ABC转运体;单核苷酸多态性;药物耐药;预后;疾病易感性
DO:10.3969/j.isn.1672-7347.2011.10.002
Date of reception 2011-08-20
Biography YIN Jiye, Ph. D. mainly engaged in the research of pharmacogenetics
Corresponding author ZHANG Jianting, E-mail: jianzhan@ iupui. edu
Foundation items This work was supported by a grant from NH (ROI CA120221) and China Scholarship Council and Scholarship Award
for Excellent Doctoral Student granted by Ministry of Education of China.