PDF(Pubmed)
Abstract：
Spontaneous coronary artery dissection (SCAD) is a significant cause of acute myocardial infarction that is increasingly recognized in young and middle-aged women. The etiology of SCAD is likely multifactorial and may include the interaction of environmental and individual factors. Here, we summarize the current understanding of the genetic factors contributing to the development of SCAD.
The molecular findings underlying SCAD have been demonstrated to include a combination of rare DNA sequence variants with large effects, common variants contributing to a complex genetic architecture, and variants with intermediate impact. The genes associated with SCAD highlight the role of arterial cells and their extracellular matrix in the pathogenesis of the disease and shed light on the relationship between SCAD and other disorders, including fibromuscular dysplasia and connective tissue diseases. While up to 10% of affected individuals may harbor a rare variant with large effect, SCAD most often presents as a complex genetic condition. Analyses of larger and more diverse cohorts will continue to improve our understanding of risk susceptibility loci and will also enable consideration of the clinical utility of genetic testing strategies in the management of SCAD.
The molecular findings underlying SCAD have been demonstrated to include a combination of rare DNA sequence variants with large effects, common variants contributing to a complex genetic architecture, and variants with intermediate impact. The genes associated with SCAD highlight the role of arterial cells and their extracellular matrix in the pathogenesis of the disease and shed light on the relationship between SCAD and other disorders, including fibromuscular dysplasia and connective tissue diseases. While up to 10% of affected individuals may harbor a rare variant with large effect, SCAD most often presents as a complex genetic condition. Analyses of larger and more diverse cohorts will continue to improve our understanding of risk susceptibility loci and will also enable consideration of the clinical utility of genetic testing strategies in the management of SCAD.
摘要：
目的：自发性冠状动脉夹层（SCAD）是急性心肌梗塞的重要原因，在中青年女性中越来越受到重视。SCAD的病因可能是多因素的，可能包括环境因素和个体因素的相互作用。这里,我们总结了目前对SCAD发生发展的遗传因素的理解。
结果：SCAD的分子发现已被证明包括具有巨大影响的罕见DNA序列变体的组合，导致复杂遗传结构的常见变异，和具有中等影响的变体。与SCAD相关的基因强调了动脉细胞及其细胞外基质在疾病发病机理中的作用，并阐明了SCAD与其他疾病之间的关系。包括纤维肌发育不良和结缔组织疾病。虽然高达10％的受影响的个体可能会有一个罕见的变异与大的影响，SCAD通常表现为复杂的遗传状况。对更大，更多样化的队列的分析将继续提高我们对风险易感性基因座的理解，并且还将考虑遗传检测策略在SCAD管理中的临床实用性。
结果：SCAD的分子发现已被证明包括具有巨大影响的罕见DNA序列变体的组合，导致复杂遗传结构的常见变异，和具有中等影响的变体。与SCAD相关的基因强调了动脉细胞及其细胞外基质在疾病发病机理中的作用，并阐明了SCAD与其他疾病之间的关系。包括纤维肌发育不良和结缔组织疾病。虽然高达10％的受影响的个体可能会有一个罕见的变异与大的影响，SCAD通常表现为复杂的遗传状况。对更大，更多样化的队列的分析将继续提高我们对风险易感性基因座的理解，并且还将考虑遗传检测策略在SCAD管理中的临床实用性。
