P727 Genome-wide methylation profiling of Crohn’s disease in women
N. Duijvis*1, A. Li Yim2, 3, J. Zhao1, W. de Jonge1, A. Mul2, G. D’Haens4, A. te Velde1, P. Henneman2
1Academic Medical Centre (AMC), Tytgat Institute for Liver and Intestinal Research, Amsterdam, Netherlands, 2Academic Medical Centre, Department of Clinical Genetics, Amsterdam, Netherlands, 3GlaxoSmithKline, Epinova Epigenetics DPU, Stevenage, United Kingdom, 4Academic Medical Centre (AMC), Department of Gastroenterology, Amsterdam, Netherlands
Crohn’s disease (CD) is a chronic inflammatory disorder of the gastrointestinal tract. Genome-wide association studies (GWAS) have identified CD-associated loci, explaining up to 25% of the heritability. A growing body of literature suggests that additional factors such as diet, the gut microbiome and the epigenome play an important part in the development and progression of CD. Here we aimed to assess differences in DNA methylation of whole blood in female CD subjects.
Whole blood was obtained from 15 female subjects that visited the outpatient clinic of the Academical Medical Centre (AMC), Amsterdam, the Netherlands. All patients (mean age ± standard deviation: 30.5 ± 6.5 years) had histologically confirmed intestinal disease. Five patients used biologicals (infliximab or adalimumab). CD patients were compared with 28 healthy controls. To measure the DNA methylation landscape, the Illumina HumanMethylation 450 k BeadChip was used.
Our analysis implicated 4 509 differentially methylated positions ([DMPs] corrected p < 0.05), of which 33 were linked to genes previously associated to CD. By performing gene ontology (GO) enrichment analysis on the DMP-associated genes, significantly enriched biological processes were revealed with notable hits for immune response, leucocyte activation and neutrophil chemotaxis (corrected p < 0.05). In addition to DMPs, differentially methylated regions (DMRs) were also assessed as groups of 2 or more consecutive DMPs. In total, we found 48 DMRs, with notable DMRs within genes involved in immunoregulation (such as HLA-J) modifying the epigenome (such as HDAC4). A number of DMPs and DMRs have been validated through MiSEQ amplicon sequencing.
Our study shows a clear association of the methylation landscape from whole blood with CD in adult females. Future studies will assess how these can affect the transcriptional regulation of their associated genes, and work towards a better understanding of the role of epigenetics into the aetiology of CD.