Abstract：
OBJECTIVE: Spontaneous coronary artery dissection (SCAD) has been increasingly recognized as a significant cause of acute myocardial infarction (AMI) in young and middle-aged women and arises through mechanisms independent of atherosclerosis. SCAD has a multifactorial etiology that includes environmental, individual, and genetic factors distinct from those typically associated with coronary artery disease. Here, we summarize the current understanding of the genetic factors contributing to the development of SCAD and highlight those factors which differentiate SCAD from atherosclerotic coronary artery disease.
RESULTS: Recent studies have revealed several associated variants with varying effect sizes for SCAD, giving rise to a complex genetic architecture. Associated genes highlight an important role for arterial cells and their extracellular matrix in the pathogenesis of SCAD, as well as notable genetic overlap between SCAD and other systemic arteriopathies such as fibromuscular dysplasia and vascular connective tissue diseases. Further investigation of individual variants (including in the associated gene PHACTR1) along with polygenic score analysis have demonstrated an inverse genetic relationship between SCAD and atherosclerosis as distinct causes of AMI. SCAD represents an increasingly recognized cause of AMI with opposing clinical and genetic risk factors from that of AMI due to atherosclerosis, and it is often associated with complex underlying genetic conditions. Genetic study of SCAD on a larger scale and with more diverse cohorts will not only further our evolving understanding of a newly defined genetic spectrum for AMI, but it will also inform the clinical utility of integrating genetic testing in AMI prevention and management moving forward.
RESULTS: Recent studies have revealed several associated variants with varying effect sizes for SCAD, giving rise to a complex genetic architecture. Associated genes highlight an important role for arterial cells and their extracellular matrix in the pathogenesis of SCAD, as well as notable genetic overlap between SCAD and other systemic arteriopathies such as fibromuscular dysplasia and vascular connective tissue diseases. Further investigation of individual variants (including in the associated gene PHACTR1) along with polygenic score analysis have demonstrated an inverse genetic relationship between SCAD and atherosclerosis as distinct causes of AMI. SCAD represents an increasingly recognized cause of AMI with opposing clinical and genetic risk factors from that of AMI due to atherosclerosis, and it is often associated with complex underlying genetic conditions. Genetic study of SCAD on a larger scale and with more diverse cohorts will not only further our evolving understanding of a newly defined genetic spectrum for AMI, but it will also inform the clinical utility of integrating genetic testing in AMI prevention and management moving forward.
摘要：
目的：自发性冠状动脉夹层（SCAD）已越来越被认为是中青年女性急性心肌梗死（AMI）的重要原因，并通过独立于动脉粥样硬化的机制产生。SCAD具有多因素病因，包括环境，个人,和遗传因素不同于通常与冠状动脉疾病相关的因素。这里,我们总结了目前对SCAD发生的遗传因素的认识,并强调了将SCAD与动脉粥样硬化性冠状动脉疾病区分开来的因素.
结果：最近的研究揭示了几种SCAD效应大小不同的相关变异，产生复杂的遗传结构。相关基因强调了动脉细胞及其细胞外基质在SCAD发病机制中的重要作用。以及SCAD与其他全身性动脉病变（如纤维肌性发育不良和血管结缔组织疾病）之间的显着遗传重叠。对个体变异（包括相关基因PHACTR1）的进一步研究以及多基因评分分析已证明SCAD和动脉粥样硬化之间的反向遗传关系是AMI的不同原因。SCAD代表了日益公认的AMI病因，与动脉粥样硬化引起的AMI具有相反的临床和遗传风险因素，它通常与复杂的潜在遗传条件有关。在更大范围和更多样化的队列中对SCAD进行遗传研究不仅会进一步加深我们对AMI新定义的遗传谱的理解。但它也将告知在AMI预防和管理中整合基因检测的临床实用性。
结果：最近的研究揭示了几种SCAD效应大小不同的相关变异，产生复杂的遗传结构。相关基因强调了动脉细胞及其细胞外基质在SCAD发病机制中的重要作用。以及SCAD与其他全身性动脉病变（如纤维肌性发育不良和血管结缔组织疾病）之间的显着遗传重叠。对个体变异（包括相关基因PHACTR1）的进一步研究以及多基因评分分析已证明SCAD和动脉粥样硬化之间的反向遗传关系是AMI的不同原因。SCAD代表了日益公认的AMI病因，与动脉粥样硬化引起的AMI具有相反的临床和遗传风险因素，它通常与复杂的潜在遗传条件有关。在更大范围和更多样化的队列中对SCAD进行遗传研究不仅会进一步加深我们对AMI新定义的遗传谱的理解。但它也将告知在AMI预防和管理中整合基因检测的临床实用性。
