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个性化心血管医学的前景:基因组学的影响

Prospects for personalized cardiovascular medicine: the impact of genomics.

作者信息

Ginsburg Geoffrey S, Donahue Mark P, Newby L Kristin

机构信息

Division of Cardiovascular Medicine, Department of Medicine, Institute for Genome Sciences & Policy, Center for Genomic Medicine, Duke University, Durham, North Carolina 27708, USA.

出版信息

J Am Coll Cardiol. 2005 Nov 1;46(9):1615-27. doi: 10.1016/j.jacc.2005.06.075. Epub 2005 Oct 10.

Abstract

Sequencing of the human genome has ushered in prospects for individualizing cardiovascular health care. There is growing evidence that the practice of cardiovascular medicine might soon have a new toolbox to predict and treat disease more effectively. The Human Genome Project has spawned several important "omic" technologies that allow "whole genome" interrogation of sequence variation (re-sequencing, genotyping, comparative genome hybridization), transcription (expression profiling, tissue arrays), proteins (gas or liquid chromatography and tandem mass spectroscopy [MS]), and metabolites (MS or nuclear magnetic resonance profiling); deoxyribonucleic acid, ribonucleic acid, protein, and metabolic approaches all provide more exacting detail of cardiovascular disease mechanisms and, in some cases, are redefining its taxonomy. Pharmacogenomic approaches are emerging across broad classes of cardiovascular therapeutics to assist practitioners in making more precise decisions about which drugs to give to which patients to optimize the benefit-to-risk ratio. Molecular imaging is developing chemical and biological probes that can sense molecular pathway mechanisms that will allow us to monitor health and disease. Together, these tools will enable a paradigm shift from genetic medicine--on the basis of the study of individual inherited characteristics, most often single genes--to genomic medicine, which by its nature is comprehensive and focuses on the functions and interactions of multiple genes and gene products, among themselves and with their environment. The information gained from such analyses, in combination with clinical data, is now allowing us to assess individual risks and guide clinical management and decision-making, all of which form the basis for cardiovascular genomic medicine.

摘要

人类基因组测序为心血管疾病的个性化医疗带来了希望。越来越多的证据表明,心血管医学实践可能很快会拥有一个新的工具包,从而更有效地预测和治疗疾病。人类基因组计划催生了几种重要的“组学”技术,这些技术可对序列变异(重测序、基因分型、比较基因组杂交)、转录(表达谱分析、组织芯片)、蛋白质(气相或液相色谱以及串联质谱[MS])和代谢物(MS或核磁共振谱分析)进行“全基因组”检测;脱氧核糖核酸、核糖核酸、蛋白质和代谢方法都提供了关于心血管疾病机制更精确的细节,并且在某些情况下正在重新定义其分类法。药物基因组学方法正在广泛应用于各类心血管治疗领域,以帮助从业者更精确地决定给哪些患者使用哪些药物,从而优化效益风险比。分子成像正在开发能够检测分子通路机制的化学和生物探针,这将使我们能够监测健康和疾病状况。总之,这些工具将促成从基因医学——基于对个体遗传特征(大多数情况下是单个基因)的研究——到基因组医学的范式转变,基因组医学本质上是全面的,侧重于多个基因及其产物之间以及它们与环境之间的功能和相互作用。从这些分析中获得的信息,结合临床数据,现在使我们能够评估个体风险并指导临床管理和决策,所有这些构成了心血管基因组医学的基础。

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