title: An integrated epigenetic and transcriptomic analysis reveals distinct tissue-specific patterns of DNA methylation associated with atopic dermatitis.
abstract: Epigenetic alterations are increasingly recognized as mechanisms for disease-associated changes in genome function and important risk factors for complex diseases. The epigenome differs between cell types and so far has been characterized in few human tissues only. In order to identify disease-associated DNA methylation differences for atopic dermatitis (AD), we investigated DNA from whole blood, T cells, B cells, as well as lesional and non-lesional epidermis from AD patients and healthy controls. To elicit functional links, we examined epidermal mRNA expression profiles. No genome-wide significant DNA methylation differences between AD cases and controls were observed in whole blood, T cells, and B cells, and, in general, intra-individual differences in DNA methylation were larger than interindividual differences. However, striking methylation differences were observed between lesional epidermis from patients and healthy control epidermis for various CpG sites, which partly correlated with altered transcript levels of genes predominantly relevant for epidermal differentiation and innate immune response. Significant DNA methylation differences were discordant in skin and blood samples, suggesting that blood is not an ideal surrogate for skin tissue. Our pilot study provides preliminary evidence for functionally relevant DNA methylation differences associated with AD, particularly in the epidermis, and represents a starting point for future investigations of epigenetic mechanisms in AD.
authors.affiliation: Department of Dermatology, Allergology, and Venereology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany; These authors contributed equally to this work.
authors.forename: Elke
authors.initials: E
authors.lastname: Rodríguez
authors.affiliation: Department of Dermatology, Allergology, and Venereology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany; Graduate School of Information Science in Health (GSISH), Technische Universität München, Munich, Germany.
authors.forename: Hansjörg
authors.initials: H
authors.lastname: Baurecht
authors.affiliation: Department of Dermatology and Allergology, Klinikum am Biederstein, Technische Universität München, Munich, Germany.
authors.forename: Anna Franziska
authors.initials: AF
authors.lastname: Wahn
authors.affiliation: Graduate School of Information Science in Health (GSISH), Technische Universität München, Munich, Germany; Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Kretschmer
authors.affiliation: Department of Dermatology, Allergology, and Venereology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.
authors.forename: Melanie
authors.initials: M
authors.lastname: Hotze
authors.affiliation: Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
authors.forename: Sonja
authors.initials: S
authors.lastname: Zeilinger
authors.affiliation: Hannover Unified Biobank, Hannover Medical School, Hannover, Germany.
authors.forename: Norman
authors.initials: N
authors.lastname: Klopp
authors.affiliation: Hannover Unified Biobank, Hannover Medical School, Hannover, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Illig
authors.affiliation: Institute of Human Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Schramm
authors.affiliation: Institute of Human Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
authors.forename: Holger
authors.initials: H
authors.lastname: Prokisch
authors.affiliation: Institute of Genetic Epidemiology, Helmholtz Zentrum Munchen, German Research Center for Environmental Health, Neuherberg, Germany.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Kühnel
authors.affiliation: Institute of Genetic Epidemiology, Helmholtz Zentrum Munchen, German Research Center for Environmental Health, Neuherberg, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Gieger
authors.affiliation: Department of Dermatology, Allergology, and Venereology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Harder
authors.affiliation: Department of Dermatology and Allergology, Klinikum am Biederstein, Technische Universität München, Munich, Germany.
authors.forename: Liliana
authors.initials: L
authors.lastname: Cifuentes
authors.affiliation: Department of Dermatology, University of Bonn, Bonn, Germany.
authors.forename: Natalija
authors.initials: N
authors.lastname: Novak
authors.affiliation: Department of Dermatology, Allergology, and Venereology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany. Electronic address: sweidinger@dermatology.uni-kiel.de.
authors.forename: Stephan
authors.initials: S
authors.lastname: Weidinger
mesh_terms: D000328:Adult; D000368:Aged; D001402:B-Lymphocytes / Q000276:immunology; D018899:CpG Islands / Q000235:genetics / Q000276:immunology; D019175:DNA Methylation / Q000235:genetics* / Q000276:immunology*; D003876:Dermatitis, Atopic / Q000235:genetics* / Q000276:immunology*; D004817:Epidermis / Q000276:immunology; D044127:Epigenesis, Genetic / Q000235:genetics* / Q000276:immunology*; D005260:Female; D005816:Genetic Complementation Test; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology; D059467:Transcriptome / Q000235:genetics / Q000276:immunology; D055815:Young Adult
chemical_list: D012333:RNA, Messenger
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