title: Correlation between Reversal of DNA Methylation and Clinical Symptoms in Psoriatic Epidermis Following Narrow-Band UVB Phototherapy.
abstract: Epigenetic modifications by DNA methylation are associated with a wide range of diseases. Previous studies in psoriasis have concentrated on epigenetic changes in immune cells or in total skin biopsies that include stromal-associated changes. In order to improve our understanding of the role of DNA methylation in psoriasis, we sought to obtain a comprehensive DNA methylation signature specific for the epidermal component of psoriasis and to analyze methylation changes during therapy. Genome-wide DNA methylation profiling of epidermal cells from 12 patients undergoing narrow-band UVB phototherapy and 12 corresponding healthy controls revealed a distinct DNA methylation pattern in psoriasis compared with controls. A total of 3,665 methylation variable positions (MVPs) were identified with an overall hypomethylation in psoriasis patient samples. DNA methylation pattern was reversed at the end of phototherapy in patients showing excellent clinical improvement. Only 7% of phototherapy-affected MVPs (150 out of 2,108) correlate with nearby gene expression. Enrichment of MVPs in enhancers indicates tissue-specific modulation of the transcriptional regulatory machinery in psoriasis. Our study identified key epigenetic events associated with psoriasis pathogenesis and helps understand the dynamic DNA methylation landscape in the human genome.
authors.affiliation: Department of Medical Biosciences/Pathology, Umeå University, Umeå, Sweden. Electronic address: xiaolian.gu@medbio.umu.se.
authors.forename: Xiaolian
authors.initials: X
authors.lastname: Gu
authors.affiliation: Department of Public Health and Clinical Medicine/Dermatology and Venereology, Umeå University, Umeå, Sweden.
authors.forename: Elisabet
authors.initials: E
authors.lastname: Nylander
authors.affiliation: Tayside Tissue Bank, Ninewells Hospital, University of Dundee, Dundee, UK.
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Coates
authors.affiliation: Institut de Génétique Moléculaire, Université Paris 7, Louis, Paris, France.
authors.forename: Robin
authors.initials: R
authors.lastname: Fahraeus
authors.affiliation: Department of Medical Biosciences/Pathology, Umeå University, Umeå, Sweden.
authors.forename: Karin
authors.initials: K
authors.lastname: Nylander
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D004247:DNA / Q000378:metabolism / Q000528:radiation effects; D019175:DNA Methylation / Q000235:genetics / Q000528:radiation effects*; D004817:Epidermis / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects*; D005260:Female; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D008875:Middle Aged; D010789:Phototherapy; D011565:Psoriasis / Q000175:diagnosis / Q000473:pathology / Q000628:therapy*; D012720:Severity of Illness Index; D016896:Treatment Outcome; D014466:Ultraviolet Rays
chemical_list: D004247:DNA
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