Abstract 11587: Intriguing Genetic Overlap Between SCAD and TAD

Abstract

Importance: Thoracic aortic dissections (TAD) are a well-known vascular cause of sudden death. Spontaneous coronary artery dissections (SCAD) are emerging as an important cause of early-onset myocardial infarction and sudden death. Genetic variants in multiple connective tissue genes have been recognized to underlie TAD; other genetic variants have similarly been recognized to underlie SCAD. Little data is available regarding any genetic commonality between TAD and SCAD. Objective: To determine any genetic overlap between genes coding for TAD and SCAD. Methods: Extensive review of 17 various retrospective and prospective clinical studies published between 2016 and 2022 exploring genetic studies of TAD and SCAD was performed using PubMed and Orbis. Articles highlighting the significant plausible triggers for TAD or SCAD were analyzed. Separate lists of causative genes were constructed for TAD and SCAD—and then commonalities sought. A Venn diagram was constructed to display the genetic overlap and common physiological pathways involved. Results: We identified a definite, meaningful overlap of fourteen independent genes based on GWAS or other genetic methods. Associated genetic pathways involved various biological processes including: Elastin degradation, smooth muscle cell function and the TGF-pathway. Overlapping genes included the following: COL3A1, TGFB2, SMAD3, MYLK, TGFBR2, TGFBR1, LOX, FBN1, NOTCH1, ELN, COL5A1, COL5A2, COL1A2, MYH11. Corresponding molecular pathways were investigated and correlated for both diseases. Conclusions and relevance: We are not aware of other studies searching for genetic commonalities between TAD and SCAD. We have successfully identified overlapping genes—and their corresponding molecular pathways—for TAD and SCAD. We hope these insights will lead to further clinical and scientific understanding of each disease via study of their fundamental commonalities.