DNA Methylation Profile Of Psoriatic Skins From Different Body Locations

Background: Psoriasis is a immune-mediated chronic inflammatory disease caused by the interplay of genetic and environmental factors.Heterogeneity has been shown between different body locations.Although studies have shown that DNA methylation patterns play an important role in the pathogenesis,comparatively analysis of DNA methylation profiles for psoriatic skin lesion obtained from extremities,back and abdomen has not been conducted.Objective: To explore whether there exist be difference in DNA methylation among different positions in psoriasis.Methods: we exploited Illumina 450 k methylation beadarrays to analysis the genome-wide methylation data with 108 psoriatic skin tissues and 57 unaffected control skin tissues.Gene Ontology and Pathway analysis were used to assess the biological function of differential methylation genes from different positions.Results: Epigenome-wide association study revealed 315,291 and 801 location-specific DMSs for back,extremities and abdomen,respectively.Moreover,these location-specific methylation genes were significantly enriched in "cell adhesion molecule binding","transcription coactivator activity",and "phosphatidylinositol binding".We also found 178 location-common differentially methylated sites and referred genes were enriched in "growth factor binding" as implicated by Gene Ontology analysis.We further observed 457 differential methylation regions,in which 23.6%,43.2% and 33.0% were mapped to back,abdomen and extremities,respectively.HOXA5 and KIAA1949 are the top overlapped differential methylation genes.Conclusions: The DNA methylation findings specific to disparate anatomical position,notably location-specific portions,which could provide new insight into the pathogenesis of psoriasis.