Heritability of aortic valve stenosis and bicuspid enrichment in families with aortic valve stenosis
Anne-Sophie Boureau, Matilde Karakachoff, Solena Le Scouarnec, Romain Capoulade, Caroline Cueff, Laure de Decker, Thomas Senage, Jean-Philippe Verhoye, Christophe Baufreton, Jean-Christian Roussel, Christian Dina, Vincent Probst, Jean-Jacques Schott, Thierry Le Tourneau, Anne-Sophie Boureau, Matilde Karakachoff, Solena Le Scouarnec, Romain Capoulade, Caroline Cueff, Laure de Decker, Thomas Senage, Jean-Philippe Verhoye, Christophe Baufreton, Jean-Christian Roussel, Christian Dina, Vincent Probst, Jean-Jacques Schott, Thierry Le Tourneau
Abstract
Background: Although a familial component of calcific aortic valve stenosis (CAVS) has been described, its heritability remains unknown. Hence, we aim to assess the heritability of CAVS and the prevalence of bicuspid aortic valve among CAVS families.
Methods: Probands were recruited following aortic valve replacement (AVR) for severe CAVS on either tricuspid (TAV) or bicuspid aortic valve (BAV). After screening, relatives underwent a Doppler-echocardiography to assess the aortic valve morphology as well as the presence and severity of CAVS. Families were classified in two types according to proband's aortic valve phenotype: TAV or BAV families. Control families were recruited and screened for the presence of BAV.
Results: Among the 2371 relatives from 138 CAVS families (pedigree cohort), heritability of CAVS was significant (h2 = 0.47, p < 0.0001), in TAV (h2 = 0.49, p < 0.0001) and BAV families (h2 = 0.50, p < 0.0001). The prevalence of BAV in 790 relatives (phenotype cohort) was significantly increased in both TAV and BAV families compared to control families with a prevalence ratio of 2.6 ([95%CI:1.4-5.9]; p = 0.005) and 4.6 ([95%CI:2.4-13.4]; p < 0.0001), respectively. At least one relative had a BAV in 22.2% of tricuspid CAVS families.
Conclusions: Our study confirms the heritability of CAVS in both TAV and BAV families, suggesting a genetic background of this frequent valvular disease. In addition, BAV enrichment in TAV families suggests an interplay between tricuspid CAVS and BAV. Overall results support the need to improve phenotyping (i.e. BAV, TAV, risk factors) in CAVS families in order to enhance the identification of rare and causal genetic variants of CAVS.
Clinical trials identifier: NCT02890407.
Keywords: Bicuspid aortic valve; Calcific aortic valve stenosis; Genetics; Heritability.
Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.
Source: PubMed