Abstract 11634: Linkage of Bicuspid Aortic Valve to a Chromosome 18q Locus is Associated With Aortic Dilation
Introduction: Bicuspid aortic valve (BAV), a congenital valve defect, is the most common cardiovascular malformation (CVM), occurring in 1-2% of humans. BAV is a clinically significant problem as it is often associated with aortic valve disease and aortic (Ao) dilation. However, the clinical impact of BAV varies greatly; some individuals require surgical intervention in childhood, others as adults, and some have minimal or no clinical implications. Little is understood of clinical factors contributing to the clinical course. Previously, we showed BAV is determined largely by genetic effects and identified a linkage signal on chromosome (chr) 18q.
Hypothesis: To test the hypothesis that genetic variation may help explain differences in clinical course, we studied families well phenotyped by echocardiography, ascertained by probands with either BAV or hypoplastic left heart syndrome and enriched for BAV.
Methods: As Ao dimensions have been shown to be increased in individuals with BAV, we used linear regression to compare dimensions in individuals from families linking to chr 18 to those not linking to chr 18. Ao dimensions normalized based on age, sex and BSA using the mean and the standard deviation from the non BAV participants, included ascending aorta (AoA), descending aorta (AoD), aortic root (AoR), sinotubular junction (STJ), aortic valve annulus (AoVA) and transverse aorta (AoT). To account for multiple testing, a threshold of 0.008 was required for significance.
Results: A total of 1143 individuals (175 with BAV) from 209 families entered the analysis. Of these, 278 individuals from 27 families linked to chr 18. We found that BAV was associated with all Ao measures except AoD (p < 0.0001 for all). Importantly, AoR and AoT exhibited significant interactions (p = 0.0013 or 0.0033), respectively) between BAV and chr18 linkage suggesting that individuals with BAV from these families had the highest measures of AoR and AoT. Further, only AoR was significantly associated with chr18 as a main effect (p = 0.0004), suggesting that AoR is elevated in chr18 families even without underlying BAV.
Conclusions: Taken together, these results suggest that the complex genetic etiology of BAV may contribute to the clinical course as manifest by Ao dilation.
Author Disclosures: L.J. Martin: None. X. Zhang: None. D. Benson: None.
- © 2014 by American Heart Association, Inc.