Heritable thoracic aortic disease (HTAD) is caused by pathogenic variations in 11 genes, although there was not enough information to stratify the risk for aortic events linked to these genes. For a study, researchers compared the risk of the first aortic event, especially the surgical repair of a thoracic aortic aneurysm or an aortic dissection, across the seven HTAD genes and variant types within each gene.
Based on the gene change, pathogenic variant type, sex, proband status, and recruitment location, the probability of first aortic events was calculated for a retrospective cohort of probands and relatives with rare variations in 7 genes for HTAD (n = 1,028).
Both the smooth muscle contraction genes (ACTA2, MYLK, and PRKG1; P=0.002) and the Loeys-Dietz syndrome genes (SMAD3, TGFB2, TGFBR1, & TGFBR2; P< 0.0001), which encode proteins in the TGF- pathway, showed significant variations in aortic event risk. Patients with variants in ACTA2, MYLK, PRKG1, and SMAD3 had a cumulative incidence of type A aortic dissection that was higher than that of elective aneurysm surgery; by contrast, patients with variants in TGFBR2 had a cumulative incidence of type A aortic dissection that was lower than that of elective aneurysm surgery. ACTA2, PRKG1, & TGFBR2 had a greater cumulative incidence of type B aortic dissection than other genes. Specific variations in ACTA2 & TGFBR2 were significantly related to a greater risk of an aortic event with juvenile-onset after controlling for proband status, sex, and recruitment site.
Data on aortic events in people with HTAD that are gene- and variant-specific help individualized aortic monitoring and clinical care.
Reference: jacc.org/doi/10.1016/j.jacc.2022.05.054
