MDR1基因多态性及其临床相关性研究进展(英文)  

MDR1 Gene Polymorphisms and Clinical Relevance

作　　者：李艳红[1] 王永华[1] 李燕[2] 杨凌[1] 

机构地区：[1]中国科学院大连化学物理研究所药用资源开发研究组,大连116023 [2]大连理工大学,大连116012

出　　处：《Acta Genetica Sinica》2006年第2期93-104,共12页

基　　金：This work was supported by the 973 Program (No.2003CCA03400) and the 863 Program (No.2003AA223061) of Ministry of Sci-ence and Technology of China

摘　　要：体内外研究证明,人体中p-gp在药物的吸收、分布、代谢和排泄(ADME)过程中发挥了非常重要的作用。多药耐药基因MDR1(ABCB1)是p-gp的编码基因。药物基因组学和遗传药理学研究发现在不同个体中MDR1基因多态性与P-gp表达和功能的改变密切相关,而且这些多态位点存在基因型分布和等位基因频率的种族差异性。近几年,己陆续发现在MDR1基冈中有50处单核苷酸多态性(SNPs)和3处插入与缺失多态性。随后,大量文献报道某些位点的SNPs如C3435T会使个体患病的易感性增加。因此人们相信,深入研究MDR1基因多态性与P-gp的生理和生化方面的相关性将对个体医疗有着非常深远的意义。文章总结了国外最新的研究进展并结合本实验室的工作着重讨论了4个方面：1)P-gp对药代动力学性质的影响；2)MDR1基因多态性及其对遗传药理学性质的影响;3)MDR1C3435T的单核苷酸多态性与P-gp表达和功能之间的相关性；4)MDR1基因多态性与人类某些疾病之间的相关性。In vivo and in vitro studies have demonstrated that P-glycoprotein （P-gp） plays a very significant role in the ADME processes （absorption, distribution, metabolism, excretion） and drug-drug interaction （DDI） of drugs in humans. P-gp is the product of multidrug resistance gene （MDR I/ABCBI）. Pharmacogenomics and pharmacogenetics studies have revealed that genetic polymorphisms of MDR1 are associated with alteration in P-gp expression and function in different ethnicities and subjects. By now, 50 single nucleotide polymorphisms （SNPs） and 3 insertion/deletion polymorphisms have been found in the MDR1 gene. Some of them, such as C3435T, have been identified to be a risk factor for numerous diseases. It is believed that further understanding of the physiology and biochemistry of P-gp with respect to its genetic variations may be important for individualized pharmacotherapy. Therefore, based on the latest public information and our studies, this review focuses on the following four aspects： 1 ） the impact of P-gp on pharmacokinetics; 2） MDR1 genetic polymorphisms and their impacts on pharmacogenetics; 3） relationship between altered P-gp expression and function and the MDR1^C3435T SNP, and 4） relevance of MDR1 polymorphisms to certain human diseases.

关 键 词：P糖蛋白 MDR1 遗传多态性 遗传药理学 

分 类 号：R346[医药卫生—基础医学]