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The Genetics of Inheritable Aortic Diseases

  • Genetics (A.T. Owens and N. Reza, Section Editors)
  • Published:
Current Cardiovascular Risk Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

Over the past 2 decades, our understanding of the role of genetics in the development and progression of aortic disease has grown considerably. This review serves as a foundational text for the reader to gain a thorough understanding of the basics of this emerging field while also displaying the latest breakthroughs which have had, and will continue to have, important impacts on clinical decision-making and patient outcomes. This review focuses on aneurysmal disease, arguably the richest subgroup of aortic diseases for genetic research.

Recent Findings

Thoracic aortic aneurysm and dissection (TAAD) is driven primarily by genetic factors. Genetic variants which drive TAAD tend to occur in genes involved in the structure and function of the aortic wall, specifically the extracellular matrix, TGF-β pathway, and smooth muscle cell contractile units. At least 37 gene variants (pathological or of unknown significance) have been found to be directly associated with the development of TAAD, independent of traditional cardiovascular (CV) risk factors such as smoking and hypertension. The standard suggestion for definitive treatment is prophylactic surgery at an aortic diameter of 5.0–5.5 cm, but several gene variants have been shown to dissect commonly at much smaller diameters (such as TGFβR1/2 or ACTA2), and so mutation-specific guidelines are leading to earlier surgery and better patient outcomes in these aggressive cases.

Abdominal aortic aneurysms (AAAs) also have a genetic component, but these are primarily driven by CV risk factors. Many gene variants have been found which are closely associated with these risk factors, such as those in the lipid metabolism pathway (SORT1). Four variants have been found through GWAS studies to directly influence AAAs independent of general risk factors, though the clinical implications are yet unclear.

Summary

New variants are discovered every year, and each creates a new avenue of research. As more data is collected on patients with each variant, such as the rate of growth, mode of inheritance, age at dissection, and diameter at dissection, we can craft more patient-specific guidelines for different subgroups of affected individuals, with the aim of achieving better long-term survival.

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  1. Cambridge University Hospitals, Cambridge, UK

    Asanish Kalyanasundaram

  2. Aortic Institute at Yale-New Haven, 789 Howard Avenue, New Haven, CT, 06510, USA

    John Elefteriades

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  1. Asanish Kalyanasundaram
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Correspondence to John Elefteriades.

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John Elefteriades is Principal of CoolSpine, serves on the Data and Safety Monitoring Board of Terumo, and consults for CryoLife. Asanish Kalyanasundaram declares no conflict of interest.

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Kalyanasundaram, A., Elefteriades, J. The Genetics of Inheritable Aortic Diseases. Curr Cardiovasc Risk Rep 16, 13–24 (2022). https://doi.org/10.1007/s12170-022-00687-x

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