Genetic architecture of thoracic aortic dissection in the female population

Sex-related differences in cardiovascular disease are now gaining much more attention and their importance is increasingly being recognized, but little is known about the genetic distribution, genotype-phenotype correlation, and outcomes in the female population with thoracic aortic dissection (TAD).

One hundred seventy-nine Chinese female probands with TAD were enrolled from Tongji Hospital between October 2009 and October 2020. Genetic analysis was performed among 12 genes, and participants were subsequently followed up for a median of 38.2 months for TAD-related death.

We identified 18 pathogenic or likely pathogenic variants among 18 (10.1%) probands and 21 variants of uncertain significance in 21 (11.7%) patients. Individuals with positive variants presented with a significant risk of TAD (OR: 12.0, 95% CI: 5.87-26.8), and an association between FBN1 (p = 2.60E-11, OR = 19.8), MYLK (p = 0.006, OR = 14.0) variants and an increased risk for female TAD was identified as well. Furthermore, nearly half of the variants were found in the FBN1 gene, which was significantly linked to early aortic dissection and tended to cause death at a young age.

This study revealed the monogenic contribution of known TAD genes to the female TAD population with East Asian ancestry. Patients who tested positive for FBN1 were significantly younger at the time of aortic dissection and had a higher probability of dying at an early age.