MDR1基因多态性及其临床相关性研究进展.pdf

遗 传 学 报 Acta Genetica Sinica , February 2006, 33 (2)：93–104 ISSN 0379-4172 MDR 1 Gene Polymorphisms and Clinical Relevance 1 1 2 1,① LI Yan-Hong , WANG Yong-Hua , LI Yan , YANG Ling 1. Laboratory of Pharmaceutical Resource Discovery, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China; 2. School of Chemical Engineering, Dalian University of Technology, Dalian 116012, China Abstract: 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 1/ABCB 1). Pharmacogenomics and pharmacogenetics studies have revealed that genetic poly- morphisms of MDR 1 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 MDR 1 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) MDR 1 genetic polymorphisms and their impacts on pharmacogenetics; 3) relationship between al- C3435T tered P-gp expression and function and the MDR 1 SNP, and 4) relevanc