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基因组学:阐明钙化性主动脉瓣狭窄病因的下一步。

Genomics: the next step to elucidate the etiology of calcific aortic valve stenosis.

作者信息

Bossé Yohan, Mathieu Patrick, Pibarot Philippe

机构信息

Department of Anatomy and Physiology, Laval Hospital Research Center, Laval University, Quebec City, Quebec, Canada.

出版信息

J Am Coll Cardiol. 2008 Apr 8;51(14):1327-36. doi: 10.1016/j.jacc.2007.12.031.

Abstract

With the current shift toward an older population, calcific aortic valve stenosis (AVS) is likely to become a major societal and economic burden. For many years, AVS was regarded as a degenerative and nonmodifiable process. However, molecular studies unanimously demonstrated that AVS is an actively regulated disorder with several potential therapeutic targets. Many factors are predicted to cause AVS, and an important genetic predisposition is anticipated. In this review, we describe candidate genes and signaling pathways identified by genetic research and incorporate this new knowledge into a more comprehensive picture of factors involved in the pathogenesis of AVS. We also emphasize the need for additional studies to elucidate its complete genetic architecture. Recent advances in genomic research offer a remarkable opportunity to investigate AVS at the most fundamental level. The benefits of these new approaches can be observed in many complex diseases, but the field of AVS is trailing behind. We discuss the future utility of these new genomic approaches to improve our understanding of AVS and to refine the management of patients in terms of diagnosis, prevention, and treatment.

摘要

随着当前人口老龄化趋势的加剧,钙化性主动脉瓣狭窄(AVS)很可能成为一项重大的社会和经济负担。多年来,AVS一直被视为一种退行性且不可改变的过程。然而,分子研究一致表明,AVS是一种受到积极调控的疾病,存在多个潜在治疗靶点。预计有多种因素会导致AVS,并且人们预期存在重要的遗传易感性。在本综述中,我们描述了通过基因研究确定的候选基因和信号通路,并将这些新知识融入到关于AVS发病机制所涉及因素的更全面图景中。我们还强调需要进行更多研究以阐明其完整的遗传结构。基因组研究的最新进展为在最基础层面研究AVS提供了绝佳机会。这些新方法的益处已在许多复杂疾病中得到体现,但AVS领域却落在了后面。我们讨论了这些新基因组方法在未来的实用性,以增进我们对AVS的理解,并在诊断、预防和治疗方面优化患者管理。

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