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P652. Global DNA methylation in inflammatory bowel disease

E. McDermott1, C. Rowan1, T. Murphy1, K. Byrne1, G. Doherty1, G. Cullen1, H. Mulcahy1, E. Ryan1, 1St. Vincent's University Hospital, Department of Gastroenterology, Dublin, Ireland

Background

The pathogenesis of IBD is widely accepted to involve interactions between environmental influences in genetically susceptible individuals. Epigenetics is the mechanism of regulation of DNA, without altering the underlying DNA sequence, and may explain at least some of the interactions between the environment and genetics that result in disease. DNA methylation is one mechanism of epigenetic regulation that involves the addition of a methyl group to a cytosine residue in a CpG site that results in silencing of that gene. It has been demonstrated to be involved in cancer and autoimmune diseases and interest in DNA methylation in disease pathogenesis, as a biomarker and, due to its reversible nature, as a treatment target, is growing. However, little is known about DNA methylation in IBD. Thus the aim of our study is to examine the association between inflammatory bowel disease and global DNA methylation.

Methods

183 individuals were recruited to this study; 40 non-IBD controls and 143 IBD patients (84 Male, 83 Crohn's disease, median age at study 35 years, median disease duration 6.8 years). Patients donated a blood sample and completed a comprehensive questionnaire containing demographic, disease-related and psychosocial variables. Patients were also independently assessed by a physician, who documented disease activity. Peripheral blood mononuclear cells from each patient were isolated and DNA extracted using standard techniques. Global DNA methylation was assessed using the MethylFlash Methylated DNA Quantification Kit by Epigentek. Patients were followed up for a median of 14 months.

Results

DNA methylation decreased with increasing patient age (r = −0.21, p = 0.02). The median global methylation was 1.19 (interquartile range (IQR 0.81–1.8) in controls and 1.69 (IQR 0.84–2.6) in IBD patients. Methylation increased in a stepwise fashion as disease activity increased (p = 0.003), Figure 1.

No other demographic or disease related factors were associated with methylation. Regression analysis demonstrated that both age and disease activity were independently associated with methylation status. On follow-up, high methylation levels (>/1.5 ng) were associated with use of biologics and requirements for surgery (p < 0.001).

Figure 1. Global methylation and disease activity.

Conclusion

Methylation patterns are significantly associated with both the presence and activity of IBD and predict a more aggressive disease course over 1 year follow-up. This may have important implications in the pathogenesis and treatment of IBD and merits further research.