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挖掘人类基因组:解读药物不良反应的当前进展

Digging up the human genome: current progress in deciphering adverse drug reactions.

作者信息

Su Shih-Chi, Chung Wen-Hung, Hung Shuen-Iu

机构信息

Department of Dermatology, Drug Hypersensitivity Clinical and Research Center, Chang Gung Memorial Hospital, 199 Tung-Hwa North Road, Taipei 105, Taiwan.

Department of Dermatology, Drug Hypersensitivity Clinical and Research Center, Chang Gung Memorial Hospital, 199 Tung-Hwa North Road, Taipei 105, Taiwan ; College of Medicine, Chang Gung University, 259 Wen-Hua First Road, Taoyuan 333, Taiwan.

出版信息

Biomed Res Int. 2014;2014:824343. doi: 10.1155/2014/824343. Epub 2014 Mar 10.

Abstract

Adverse drug reactions (ADRs) are a major clinical problem. In addition to their clinical impact on human health, there is an enormous cost associated with ADRs in health care and pharmaceutical industry. Increasing studies revealed that genetic variants can determine the susceptibility of individuals to ADRs. The development of modern genomic technologies has led to a tremendous advancement of improving the drug safety and efficacy and minimizing the ADRs. This review will discuss the pharmacogenomic techniques used to unveil the determinants of ADRs and summarize the current progresses concerning the identification of biomarkers for ADRs, with a focus on genetic variants for genes encoding drug-metabolizing enzymes, drug-transporter proteins, and human leukocyte antigen (HLA). The knowledge gained from these cutting-edge findings will form the basis for better prediction and management for ADRs, ultimately making the medicine personalized.

摘要

药物不良反应(ADR)是一个重大的临床问题。除了对人类健康产生临床影响外,医疗保健和制药行业中与ADR相关的成本也非常巨大。越来越多的研究表明,基因变异可决定个体对ADR的易感性。现代基因组技术的发展极大地推动了提高药物安全性和疗效以及最大限度减少ADR方面的进步。本综述将讨论用于揭示ADR决定因素的药物基因组学技术,并总结目前在鉴定ADR生物标志物方面的进展,重点关注编码药物代谢酶、药物转运蛋白和人类白细胞抗原(HLA)的基因的基因变异。从这些前沿发现中获得的知识将为更好地预测和管理ADR奠定基础,最终实现医学的个性化。

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本文引用的文献

1
HLA-B*13:01 and the dapsone hypersensitivity syndrome.HLA-B*13:01 与氨苯砜超敏反应综合征。
N Engl J Med. 2013 Oct 24;369(17):1620-8. doi: 10.1056/NEJMoa1213096.
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Disease-targeted sequencing: a cornerstone in the clinic.疾病靶向测序:临床的基石。
Nat Rev Genet. 2013 Apr;14(4):295-300. doi: 10.1038/nrg3463. Epub 2013 Mar 12.
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microRNAs as mediators of drug toxicity.微小 RNA 作为药物毒性的介质。
Annu Rev Pharmacol Toxicol. 2013;53:377-400. doi: 10.1146/annurev-pharmtox-011112-140250. Epub 2012 Nov 16.

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