Peripheral blood methylation profiling of female Crohn’s disease patients

Abstract

BackgroundCrohn’s disease (CD) is a chronic inflammatory disorder belonging to the inflammatory bowel diseases (IBD). CD affects distinct parts of the gastrointestinal tract, leading to symptoms including diarrhea, fever, abdominal pain, weight loss, and anemia. The aim of this study was to assess whether the DNA methylome of peripheral blood cells can be associated with CD in women.MethodsSamples were obtained from 18 female patients with histologically confirmed ileal or ileocolic CD and 25 healthy age- and gender-matched controls (mean age and standard deviation: 30.5 ± 6.5 years for both groups). Genome-wide DNA methylation was determined using the Illumina HumanMethylation 450k BeadChip.ResultsOur analysis implicated 4287 differentially methylated positions (DMPs; corrected p < 0.05) that are associated to 2715 unique genes. Gene ontology enrichment analysis revealed significant enrichment of our DMPs in immune response processes and inflammatory pathways. Of the 4287 DMPs, 32 DMPs were located on chromosome X with several hits for MIR223 and PABPC5. Comparison with previously performed (epi)genome-wide studies revealed that we replicated 33 IBD-associated genes. In addition to DMPs, we found eight differentially methylated regions (DMRs).ConclusionsCD patients display a characteristic DNA methylation landscape, with the differentially methylated genes being implicated in immune response. Additionally, DMPs were found on chromosome X suggesting X-linked manifestations of CD that could be associated with female-specific symptoms.Electronic supplementary materialThe online version of this article (doi:10.1186/s13148-016-0230-5) contains supplementary material, which is available to authorized users.

Adipose stem cells from patients with Crohn’s disease show a distinctive DNA methylation pattern

“…PTPRN2 encodes a protein tyrosine phosphatase implicated in various biological processes including tumor pathogenesis and autoimmune disease [31][32][33][34]. Supporting our present findings, PTPRN2 has previously been reported to be the most significant DMP in PBMCs from patients with CD [19]. Interestingly, PTPRN2 shows dysregulated DNA methylation in obese children [31], pointing to a link between metabolic dysfunction and immune response.…”

“…Also, epigenetic modifications to hASCs might be reflected in peripheral blood, as already demonstrated in other inflammatory diseases such as obesity [45]. Indeed, changes to the PBMC methylome in CD have previously been described, revealing that differentially methylated genes implicated in immune response are the most frequently affected [19,46]. In agreement with these reports, we found the same enriched GO terms in hASCs in CD such as immune response and immune system process, and we found that some of the changes found in hASCs were replicated in PBMCs, even when patients were classified according to clinical status.…”

“…The constancy of this dysfunctional phenotype might reflect changes at the epigenetic level, which ultimately hamper the resolution of the inflammatory events in the sinus of the affected mesenteric AT. In support of this proposition, recent DNA methylation studies in peripheral blood mononuclear cells (PBMCs) revealed that patients with CD have a distinct DNA methylome linked to the expression of differentially methylated genes associated with immune response and inflammation [19][20][21]. We hypothesized that hASCs from patients with CD are conditioned by a chronic inflammatory milieu, which may alter their DNA methylome and influence their antiinflammatory and regenerative capacity.…”

Methyl-donor supplementation prevents intestinal colonization by Adherent-Invasive E. coli in a mouse model of Crohn’s disease

“…Folate and other methyl-donor molecules play a crucial role in the maintenance of epigenetic marks such as DNA methylation. The importance of the epigenetic component in the etiology of CD has recently been illustrated by the demonstration of modified DNA methylation profiles in patients compared to healthy subjects 5 , 7 , 9 , 12 , 42 . Furthermore, polymorphisms in the DNMT3a gene (involved in the establishment of de novo DNA methylation marks) were previously associated to an increased risk to develop CD, suggesting an important role of DNA methylation in the inflammatory process 43 .…”

Whole-Genome DNA Methylation Profiling of CD14+ Monocytes Reveals Disease Status and Activity Differences in Crohn’s Disease Patients

“…Functionally, the presence of DNA methylation in the promoter area is often inversely correlated with gene expression [9][10][11], which in certain cases was found to be a causal relationship [12,13]. Previous epigenetic studies reported differences in the DNA methylome of peripheral blood or peripheral blood mononuclear cells (PBMCs), with differentially methylated loci occurring in genes associated with inflammatory pathways [14][15][16]. Here, we sought to build on the previous studies by focusing on an individual immune cell type: monocytes.…”