Risk Factors for Aortic Valve Disease in Bicuspid Aortic Valve: A Family-Based Study

Division of Cardiology, Cincinnati Children's Hospital Medical Center, Ohio 45229-3039, USA.
American Journal of Medical Genetics Part A (Impact Factor: 2.05). 05/2011; 155A(5):1015-20. DOI: 10.1002/ajmg.a.33974
Source: PubMed

ABSTRACT Bicuspid aortic valve (BAV) is the most common cardiovascular malformation and is a risk factor for aortic valve disease (AVD). AVD typically manifests later in life, and the majority of cases have BAV. The purpose of this study was to identify risk factors for AVD in individuals with BAV. Families enriched for BAV were identified in a pediatric population, and echocardiography was performed on all family members. AVD was identified as stenosis and/or insufficiency, and BAV morphology was defined as right-left (RL), right-non (RN) or indeterminate. Heritability (h(2)) of AVD and BAV morphology was estimated using variance components analysis (SOLAR). To assess AVD risk over time, we used Generalized Estimating Equations methodology (SAS) adjusting for age and gender. A total of 1,128 individuals from 226 families were evaluated. BAV was identified in 281 individuals (25%), and AVD was identified in 167 (59%) individuals with BAV. Previously, we identified a high heritability for BAV (h(2)  = 0.89 ± 0.06, P < 0.00001), but the heritability of AVD in the present study (0.07 ± 0.17, P = 0.33) was low. AVD was significantly associated with BAV morphology (P = 0.0027) and age (P = 0.0068). Children with RN BAV and adults with RL BAV were more likely to develop AVD. BAV is determined largely by genetic effects, but the phenotypic variability of AVD is primarily determined by nongenetic factors. BAV morphology may have predictive value for the time course of AVD.


Available from: Lisa Martin, Sep 18, 2014
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    ABSTRACT: Bicuspid aortic valve (BAV) is the most common adult congenital heart defect and is found in 0.5% to 2.0% of the general population. The term “BAV” refers to a heterogeneous group of disorders characterized by diverse aortic valve malformations with associated aortopathy, congenital heart defects, and genetic syndromes. Even after decades of investigation, the genetic determinants of BAV and its complications remain largely undefined. Just as BAV phenotypes are highly variable, the genetic etiologies of BAV are equally diverse and vary from complex inheritance in families to sporadic cases without any evidence of inheritance. In this paper, the authors discuss current concepts in BAV genetics and propose a roadmap for unraveling unanswered questions about BAV through the integrated analysis of genetic and clinical data.
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