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

The Heart Surgery Forum
Asad A ShahG Chad Hughes

Abstract

Bicuspid aortic valves predispose to ascending aortic aneurysms, but the mechanisms underlying this aortopathy remain incompletely characterized.  We sought to identify epigenetic pathways predisposing to aneurysm formation in bicuspid patients. Ascending aortic aneurysm 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. Twenty-seven probes in 9 genes showed significant differential methylation and expression (P<5.5x10-4).  The top gene was protein tyrosine phosphatase, non-receptor type 22 (PTPN22), 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 patients, as compared to tricuspid patients.  Numerous genes involved in cardiovascular development were also differentially methylated, but not differentiall...Continue Reading

Citations

Apr 20, 2018·Journal of Cardiovascular Development and Disease·Froso SophocleousGiovanni Biglino
May 22, 2019·Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire·Dimple PrasherRaja B Singh
Apr 15, 2020·American Journal of Medical Genetics. Part a·Lidia PezzaniDonatella Milani
Oct 11, 2017·Frontiers in Physiology·Noor M YassineSimon C Body
Sep 30, 2018·Biophysics Reviews·Stefanie S PortelliRichmond W Jeremy
Oct 22, 2020·International Journal of Molecular Sciences·Cassandra MaleckiElizabeth N Robertson
Jun 3, 2021·International Journal of Molecular Sciences·Alejandro Junco-VicenteIsabel Rodríguez

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