P051 DNA methylation signatures associated with pathogenesis Crohn's disease-related genes
I. Moret Tatay1,2, E. Cerrillo1,3, E. Sáez-González1,3, D. Hervás4, M. Iborra1,2,3, J. Sandoval5, E. Busó6, L. Tortosa1,2, P. Nos1,2,3, B. Beltrán1,2,3
1IIS Hospital La Fe, Gastroenterology, Valencia, Spain, 2Networked Biomedical Research Centre for Hepatic and Digestive Diseases (CIBEREHD), Madrid, Spain, 3Hospital Universitari i Politècnic La Fe, Inflammatory Bowel Disease Unit, Gastroenterology Department, Valencia, Spain, 4IIS Hospital La Fe, Biostatistics, Valencia, Spain, 5IIS Hospital La Fe, Biomarkers and Precision Medicine, Valencia, Spain, 6University of Valencia, Central Unit for Research in Medicine (UCIM), Valencia, Spain
Epigenetic mechanism in Crohn's disease (CD) pathogenia is important for gene expression regulation, as complex interactions between genes and the environment occur. DNA methylation is an epigenetic mechanism that negative regulates DNA expression. However, little is known about the associations of DNA methylation and CD pathogenesis. The study of the level of methylation in CD-related genes may help to identify key elements in the pathology of CD, and to select new therapeutical targets. Therefore, we aimed to assess the DNA methylation changes on specific genes, previously related to the CD pathogenesis, and their possible associations with the pathology.
We included 31 subjects: 11 active CD (aCD) at the onset of disease and prior to any specific medication; 12 inactive CD (iCD) with clinical, analytical and morphologic remission; 8 healthy controls (CTR). DNA was obtained from peripheral blood and analysed by Sequenom. Gene-selection was based on the previous information regarding their role in CD. Candidate genes were: Catalase (CAT), α-defensin 5 (HNP-5), FasR, FasL, TNF, TNFRSF1A, TNFRSF1B, PPA2, ABCB1, NOD2, PPARγ, PKCζ. In addition, a prospective cohort of new patients and controls was recruited for the validation of results: 24 aCD; 24 iCD; 24 CTR. We used the elastic net algorithm for the statistical analysis and the R software (version 3.1.0).
We studied a total of 280 CpGs from the selected genes. Only 16 CpGs showed differential methylation profiles between the three experimental groups (aCD, iCD and CTR). From these 16 CpGs, we selected for validation those with the higher differences between aCD, iCD and CTR: HNP-5 CpG_11 and CpG_13; CAT CpG_31.32; TNF CpG_4 and CpG_12; ABCB1 CpG_6.7.8. Results validated the genes HNP-5 and TNF with
The identification of DNA methylation signatures associated with pathogenesis CD-related genes could help to improve the diagnosis and management of CD patients. The permanent increased methylation of HNP-5 gene and the permanent decreased methylation of TNF gene confer a signature for CD patients’ identification. The differential profile of methylation between aCD and iCD could be used as an activity signature. New treatments focussed on modifying those methylation signatures could be explored for CD management.
- Posted in: Poster presentations: Basic science (2019)