Objective: Bicuspid aortic valve, the most common congenital cardiac malformation, is caused by fusion of valve cushions at the onset of valvulogenesis. Although its exact pathogenesis is still unclear, a genetic basis is appearing more and more likely. Search for a potential candidate gene by reviewing semilunar valve morphogenesis led us to the ubiquitin fusion degradation 1-like gene (UFD1L), which is highly expressed in the cardiac outflow tract during embryogenesis.
Methods: Aortic valves were collected during surgery from 39 patients with bicuspid aortic valve (mean age 56.8 +/- 18.1 years) and from 38 patients with tricuspid aortic valve (mean age 61.7 +/- 16.1 years). Fluorescence in situ hybridization was performed for detection of microdeletion, quantitative reverse transcriptase-polymerase chain reaction to measure gene expression, and Western blotting to analyze the amount of UFD1L gene product.
Results: No microdeletion was found in either group in the critical region of chromosome 22 containing the UFD1L gene. UFD1L gene expression, however, was significantly reduced in bicuspid aortic valve samples (median 787-fold) relative to tricuspid aortic valve samples (median 10,887-fold, P = .001). The amount of UFD1L gene product was also significantly diminished in bicuspid aortic valve samples (3.9 +/- 2.6 vs 8.4 +/- 4.8 optical density units, P < .05).
Conclusion: Bicuspid aortic valve was associated with downregulation of UFD1L gene expression, supporting the hypothesis that bicuspid aortic valve is a genetic disorder, with the UFD1L gene as a potential candidate gene.