PDF(Pubmed)
Abstract：
Genetic predisposition to cardiac arrhythmias has been a field of intense investigation. Research initially focused on rare hereditary arrhythmias, but over the last two decades, the role of genetic variation (single nucleotide polymorphisms) in heart rate, rhythm, and arrhythmias has been taken into consideration as well. In particular, genome-wide association studies have identified hundreds of genomic loci associated with quantitative electrocardiographic traits, atrial fibrillation, and less common arrhythmias such as Brugada syndrome. A significant number of associated variants have been found to systematically localize in non-coding regulatory elements that control the tissue-specific and temporal transcription of genes encoding transcription factors, ion channels, and other proteins. However, the identification of causal variants and the mechanism underlying their impact on phenotype has proven difficult due to the complex tissue-specific, time-resolved, condition-dependent, and combinatorial function of regulatory elements, as well as their modest conservation across different model species. In this review, we discuss research efforts aimed at identifying and characterizing-trait-associated variant regulatory elements and the molecular mechanisms underlying their impact on heart rate or rhythm.
摘要：
心律失常的遗传易感性一直是研究的领域。研究最初集中在罕见的遗传性心律失常，但是在过去的二十年里，遗传变异（单核苷酸多态性）在心率中的作用，节奏,心律失常也被考虑在内。特别是,全基因组关联研究已经确定了数百个与定量心电图性状相关的基因组基因座，心房颤动,和不太常见的心律失常，如Brugada综合征。已发现大量相关变体系统地定位在控制编码转录因子的基因的组织特异性和时间转录的非编码调控元件中。离子通道,和其他蛋白质。然而,由于复杂的组织特异性，因果变异的鉴定及其对表型影响的机制已被证明是困难的，时间解决，依赖于条件，和调节元件的组合功能，以及它们在不同模型物种中的适度保护。在这次审查中,我们讨论了旨在鉴定和表征性状相关变异调节元件及其影响心率或心律的分子机制的研究工作.
