P703 Genome-wide DNA methylation changes in Ulcerative Colitis patients
T.O. Kim1, J.M. Yi2, S.B. Park*3
1University College of Medicine, Haeundae Paik Hospital, Internal Medicine, Busan, South Korea, 2Dongnam Institute of Radiological & Medical Sciences (DIRAMS), Research Center, Busan, South Korea, 3Pusan National University Yangsan Hospital, Internal Medicine, Yangsan, South Korea
Inflammatory bowel disease (IBDs), including Crohn's disease (CD) and Ulcerative colitis (UC), are emerging globally to understand its pathogenesis. The biological cause of IBD still remains unclear but evidence is accumulating that complex interactions between the genome and the gut microbiota of the host and environmental factors. Regarding the interaction between environmental and genome, epigenetic mechanism and more specifically DNA methylation seem to be of great importance.
We employed high-throughput microarray-based method for genome-wide DNA methylation profile using Illumina Infinium HumanMethylation450 BeadChip arrays. For this analysis, we used eight UC samples and three normal control colonic tissues from patients and obtained genomic DNA from biopsies. Differential methylated signal in UC were analyzed using bioinformatics tools. We also validated our candidate genes in an independent UC sample panel by MSP or bisulfite sequencing analyses.
We have identified new 70 hypermethylated genes in UC samples compared with normal controls. Surprisingly, these genes are already highly methylated in colon cancer cell lines. More interestingly, new 12 (STC2, TTC33, MYO1E, USH2A, C9orf3, FOXP2, ALOXE3, AGTR1, KLK11, PECI,HSPB6, and HS3ST3B1) out of 70 genes are hypermethylated in UC patient samples and colon cancer patients. We report first here that these genes are hypermethylated in UC patients. In addition, since we have two different groups of UC samples based on disease duration, differential methylation pattern identified clinical correlation loci in our UC samples. With our candidate hypermethylated genes in UC samples, several biological pathways are involved each other.
Our genome-wide approach could contribute to identify UC specifically hypermethylated genes therefore these genes could be great use of prognostic biomarker for this disease and also to understand biological pathogenesis of IBD disease.