Abstract
BackgroundThe bicuspid aortic valve (BAV) is prone to ascending aortic dilatation (AAD) involving both the tubular segment and the aortic root. The genetic factor was proposed as one of the most important mechanisms for AAD. We hypothesized that the rare genetic variants mainly contribute to the pathogenesis of aortic roots in affected individuals.MethodsThe diameter of aortic root or ascending aorta ≥ 40 mm was counted as AAD. The targeted next-generation sequencing of 13 BAV-associated genes were performed on a continuous cohort of 96 unrelated BAV patients. The rare variants with allele frequency < 0.05% were selected and analyzed. Variants frequency was compared against the Exome aggregation consortium database. The pathogenicity of the genetic variants was evaluated according to the American College of Medical Genetics and Genomics guidelines.ResultsA total of 27 rare nonsynonymous coding variants involving 9 genes were identified in 25 individuals. The burden analysis revealed that variants in GATA5, GATA6, and NOTCH1 were significantly associated with BAV. Eighty percent of the pathogenic variants were detected in root group. The detection rate of rare variants was higher in root dilatation group (71.4%) compared with normal aorta (29.0%) and tubular dilatation groups (29.6%) (P = 0.018). The rare variant was identified as the independent risk factor of root dilatation [P = 0.014, hazard ratio = 23.9, 95% confidence interval (1.9–302.9)].ConclusionsOur results presented a broad genetic spectrum in BAV patients. The rare variants of BAV genes contribute the most to the root phenotype among BAV patients.
Highlights
The bicuspid aortic valve (BAV) is prone to ascending aortic dilatation (AAD) involving both the tubular segment and the aortic root
By targeted generation sequencing (NGS) of genes associated with BAV, we aimed to investigate distribution of rare variants in a large well-phenotyped BAV cohort
The aortic dilatations were found in 34 patients (35.4% of all the participants), of them, 22 patients underwent surgery for the aortic aneurysm or dissection
Summary
The bicuspid aortic valve (BAV) is prone to ascending aortic dilatation (AAD) involving both the tubular segment and the aortic root. The genetic factor was proposed as one of the most important mechanisms for AAD. Bicuspid aortic valve (BAV) is a common congenital valvular defect, affecting about 0.5–1% of the general population [1, 2]. Ma et al BMC Cardiovasc Disord (2021) 21:413 of the cause of BAV aortopathy, i.e. the hemorheological reason and genetic factors. The former argues that the fused-leaflet of BAV alters the blood flow and increases the shear stress in the tubular ascending aorta [7]. Which kind of influence would play a more important role is still controversial
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