title: Genome-Wide DNA Methylation Analysis and Epigenetic Variations Associated with Congenital Aortic Valve Stenosis (AVS).
abstract: Congenital heart defect (CHD) is the most common cause of death from congenital anomaly. Among several candidate epigenetic mechanisms, DNA methylation may play an important role in the etiology of CHDs. We conducted a genome-wide DNA methylation analysis using an Illumina Infinium 450k human methylation assay in a cohort of 24 newborns who had aortic valve stenosis (AVS), with gestational-age matched controls. The study identified significantly-altered CpG methylation at 59 sites in 52 genes in AVS subjects as compared to controls (either hypermethylated or demethylated). Gene Ontology analysis identified biological processes and functions for these genes including positive regulation of receptor-mediated endocytosis. Consistent with prior clinical data, the molecular function categories as determined using DAVID identified low-density lipoprotein receptor binding, lipoprotein receptor binding and identical protein binding to be over-represented in the AVS group. A significant epigenetic change in the APOA5 and PCSK9 genes known to be involved in AVS was also observed. A large number CpG methylation sites individually demonstrated good to excellent diagnostic accuracy for the prediction of AVS status, thus raising possibility of molecular screening markers for this disorder. Using epigenetic analysis we were able to identify genes significantly involved in the pathogenesis of AVS.
authors.affiliation: Department of Obstetrics and Gynecology, Oakland University William Beaumont School of Medicine, Royal Oak, Michigan, United States of America.
authors.forename: Uppala
authors.initials: U
authors.lastname: Radhakrishna
authors.affiliation: Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, Michigan, United States of America.
authors.forename: Samet
authors.initials: S
authors.lastname: Albayrak
authors.affiliation: Department of Obstetrics and Gynecology, Oakland University William Beaumont School of Medicine, Royal Oak, Michigan, United States of America.
authors.forename: Zeynep
authors.initials: Z
authors.lastname: Alpay-Savasan
authors.affiliation: Department of Obstetrics and Gynecology, Oakland University William Beaumont School of Medicine, Royal Oak, Michigan, United States of America.
authors.forename: Amna
authors.initials: A
authors.lastname: Zeb
authors.affiliation: Department of Obstetrics and Gynecology, Oakland University William Beaumont School of Medicine, Royal Oak, Michigan, United States of America.
authors.forename: Onur
authors.initials: O
authors.lastname: Turkoglu
authors.affiliation: Department of Obstetrics and Gynecology, Oakland University William Beaumont School of Medicine, Royal Oak, Michigan, United States of America.
authors.forename: Paul
authors.initials: P
authors.lastname: Sobolewski
authors.affiliation: Department of Obstetrics and Gynecology, Oakland University William Beaumont School of Medicine, Royal Oak, Michigan, United States of America.
authors.forename: Ray O
authors.initials: RO
authors.lastname: Bahado-Singh
mesh_terms: D001024:Aortic Valve Stenosis / Q000151:congenital* / Q000235:genetics; D016022:Case-Control Studies; D018899:CpG Islands; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005260:Female; D006801:Humans; D008297:Male