DNA Methylation Profiling in Inflammatory Bowel Disease Provides New Insights into Disease Pathogenesis

Abstract

Our data provide new insights into differential epigenetic regulation of genes and molecular pathways, which may contribute to the pathogenesis and activity of IBD.

Integrative epigenome-wide analysis demonstrates that DNA methylation may mediate genetic risk in inflammatory bowel disease

“…There were 412 DMPs when comparing CD to controls (Supplementary Table 3) and 203 when comparing UC to controls (Supplementary Table 4). As has previously been reported15, no significant differentially methylated sites were detected in a comparison of CD and UC following correction for multiple testing (Supplementary Table 5). There was a significant overlap between DMPs seen in IBD, CD and UC compared with controls (Supplementary Fig.…”

“…This is particularly interesting given the recent focus on strategies to therapeutically target leukocyte adhesion, namely vedolizumab, which targets a different integrin subunit (α4β7)35. Aberrant DNA hypermethylation at the ITGB2 locus has previous been demonstrated in IBD in mucosal14 and peripheral blood leucocyte15 samples as well as in other diseases36. The other DMRs are also of great interest: WDR8 or WRAP73 (WD (trp-asp) repeat protein family, antisense to Trp73) which is involved in several cellular and gene regulatory processes37 and TXK is discussed in below.…”

“…In the context of IBD several preliminary studies have used the Illumina 27k platform101112 and subsequently the HumanMethylation450 platform to assess genome-wide DNA methylation patterns in blood and mucosal biopsy material in IBD131415. In our own study in treatment-naive children with CD, highly significant differences in DNA methylation were noted to occur in genes implicated in disease pathogenesis16.…”

Assessing the co-variability of DNA methylation across peripheral cells and tissues: implications for the interpretation of findings in epigenetic epidemiology

“…In addition, subtle changes or differences in rarer cell types may go undetected as they compete against the background of additional variation from analysing multiple cell types simultaneously. Despite the limitations of analysing DNAm measured in bulk tissue, significant differences in DNAm have been associated with a range of exposures and phenotypes -including tobacco smoking [4][5][6][7] , body mass index 8,9 , autoimmune disorders 10,11 and psychiatric disorders 12, 13although it is unclear whether trait-associated variation is driven by the variability of DNAm in specific blood cell types.…”

Promoter Hypermethylation of GATA3, IL-4, and TGF-β Confers Susceptibility to Vogt-Koyanagi-Harada Disease in Han Chinese

“…24,25 As methylation of CpG dinucleotides is a widely accepted phenomenon occurring during the immune response, attention recently has focused on the role of epigenetic alterations in the development of autoimmune disease. [26][27][28][29] A growing body of literature has demonstrated the relationship between impaired T-cell DNA methylation and some forms of autoimmune disease. [30][31][32][33] A significant hypomethylation of T-cell DNA has been demonstrated in patients with active systematic lupus erythematosus (SLE) and rheumatoid arthritis (RA), suggesting that T-cell mediated autoimmunity contributes to the pathogenesis of these diseases.…”