BACKGROUND:    Bicuspid aortic valves predispose to ascending @entity449 , but the mechanisms underlying this aortopathy remain incompletely characterized.   We sought to identify epigenetic pathways predisposing to @entity439 formation in bicuspid @entity1 . METHODS:    Ascending aortic @entity439 tissue samples were collected at the time of aortic replacement in subjects with bicuspid and trileaflet aortic valves.   Genome-wide DNA methylation status was determined on DNA from tissue using the Illumina 450K methylation chip, and gene expression was profiled on the same samples using Illumina Whole-Genome DASL arrays.   Gene methylation and expression were compared between bicuspid and trileaflet individuals using an unadjusted Wilcoxon rank sum test.    RESULTS:    Twenty-seven probes in 9 genes showed significant differential methylation and expression (P<5.5x10-4).   The top gene was protein @entity4149 phosphatase, non-receptor type 22 ( @entity5812 ), which was hypermethylated (delta beta range: +15.4 to +16.0%) and underexpressed (log 2 gene expression intensity: bicuspid 5.1 vs. trileaflet 7.9, P=2x10-5) in bicuspid @entity1 , as compared to tricuspid @entity1 .   Numerous genes involved in cardiovascular development were also differentially methylated, but not differentially expressed, including @entity17712 (4 probes, delta beta range:   -10.0 to -22.9%), which when mutated causes the syndrome of @entity2334 and dissections CONCLUSIONS:    Using an integrated, unbiased genomic approach, we have identified novel genes associated with ascending @entity449 in @entity1 with bicuspid aortic valves, modulated through epigenetic mechanisms.   The top gene was @entity5812 , which is involved in T-cell receptor signaling and associated with various @entity1200 .   These differences highlight novel potential mechanisms of @entity439 development in the bicuspid population.

Epigenetic profiling identifies novel genes for ascending aortic XXXX formation with bicuspid aortic valves.

@entity1 :: ('9606', 'Species') :: ['patients'] @entity449 :: ('MESH:D001014', 'Disease') :: ['aortic aneurysms'] @entity17712 :: ('59', 'Gene') :: ['ACTA2'] @entity2334 :: ('MESH:D017545', 'Disease') :: ['familial thoracic aortic aneurysms'] @entity439 :: ('MESH:D000783', 'Disease') :: ['aneurysm'] @entity1200 :: ('MESH:D007154', 'Disease') :: ['immune disorders'] @entity5812 :: ('26191', 'Gene') :: ['PTPN22'] @entity4149 :: ('D014443', 'Chemical') :: ['tyrosine']
@entity439 :: (MESH:D000783,Disease) :: ['aneurysm']
