title: Alterations in cardiac DNA methylation in human dilated cardiomyopathy.
abstract: Dilated cardiomyopathies (DCM) show remarkable variability in their age of onset, phenotypic presentation, and clinical course. Hence, disease mechanisms must exist that modify the occurrence and progression of DCM, either by genetic or epigenetic factors that may interact with environmental stimuli. In the present study, we examined genome-wide cardiac DNA methylation in patients with idiopathic DCM and controls. We detected methylation differences in pathways related to heart disease, but also in genes with yet unknown function in DCM or heart failure, namely Lymphocyte antigen 75 (LY75), Tyrosine kinase-type cell surface receptor HER3 (ERBB3), Homeobox B13 (HOXB13) and Adenosine receptor A2A (ADORA2A). Mass-spectrometric analysis and bisulphite-sequencing enabled confirmation of the observed DNA methylation changes in independent cohorts. Aberrant DNA methylation in DCM patients was associated with significant changes in LY75 and ADORA2A mRNA expression, but not in ERBB3 and HOXB13. In vivo studies of orthologous ly75 and adora2a in zebrafish demonstrate a functional role of these genes in adaptive or maladaptive pathways in heart failure.
authors: Department of Internal Medicine III, University of Heidelberg, Heidelberg, Germany.
authors: Jan
authors: J
authors: Haas
authors: Karen S
authors: KS
authors: Frese
authors: Yoon Jung
authors: YJ
authors: Park
authors: Andreas
authors: A
authors: Keller
authors: Britta
authors: B
authors: Vogel
authors: Anders M
authors: AM
authors: Lindroth
authors: Dieter
authors: D
authors: Weichenhan
authors: Jennifer
authors: J
authors: Franke
authors: Simon
authors: S
authors: Fischer
authors: Andrea
authors: A
authors: Bauer
authors: Sabine
authors: S
authors: Marquart
authors: Farbod
authors: F
authors: Sedaghat-Hamedani
authors: Elham
authors: E
authors: Kayvanpour
authors: Doreen
authors: D
authors: Köhler
authors: Nadine M
authors: NM
authors: Wolf
authors: Sarah
authors: S
authors: Hassel
authors: Rouven
authors: R
authors: Nietsch
authors: Thomas
authors: T
authors: Wieland
authors: Philipp
authors: P
authors: Ehlermann
authors: Jobst-Hendrik
authors: JH
authors: Schultz
authors: Andreas
authors: A
authors: Dösch
authors: Derliz
authors: D
authors: Mereles
authors: Stefan
authors: S
authors: Hardt
authors: Johannes
authors: J
authors: Backs
authors: Jörg D
authors: JD
authors: Hoheisel
authors: Christoph
authors: C
authors: Plass
authors: Hugo A
authors: HA
authors: Katus
authors: Benjamin
authors: B
authors: Meder
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D001706:Biopsy; D002311:Cardiomyopathy, Dilated / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D016022:Case-Control Studies; D016000:Cluster Analysis; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005260:Female; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D020022:Genetic Predisposition to Disease; D057809:HEK293 Cells; D006801:Humans; D037181:Lectins, C-Type / Q000235:genetics / Q000378:metabolism; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D015778:Minor Histocompatibility Antigens; D008969:Molecular Sequence Data; D009206:Myocardium / Q000378:metabolism*; D010641:Phenotype; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D043705:Receptor, Adenosine A2A / Q000235:genetics / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D015203:Reproducibility of Results; D017422:Sequence Analysis, DNA / Q000379:methods; D020539:Sequence Analysis, Protein; D014162:Transfection; D015027:Zebrafish / Q000235:genetics / Q000378:metabolism; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D015703:Antigens, CD; C093569:DEC-205 receptor; D037181:Lectins, C-Type; D015778:Minor Histocompatibility Antigens; D012333:RNA, Messenger; D043705:Receptor, Adenosine A2A; D011956:Receptors, Cell Surface; D029961:Zebrafish Proteins