title: A Genome-Wide Methylation Approach Identifies a New Hypermethylated Gene Panel in Ulcerative Colitis.
abstract: The cause of inflammatory bowel disease (IBD) is still unknown, but there is growing evidence that environmental factors such as epigenetic changes can contribute to the disease etiology. The aim of this study was to identify newly hypermethylated genes in ulcerative colitis (UC) using a genome-wide DNA methylation approach. Using an Infinium HumanMethylation450 BeadChip array, we screened the DNA methylation changes in three normal colon controls and eight UC patients. Using these methylation profiles, 48 probes associated with CpG promoter methylation showed differential hypermethylation between UC patients and normal controls. Technical validations for methylation analyses in a larger series of UC patients (n = 79) were performed by methylation-specific PCR (MSP) and bisulfite sequencing analysis. We finally found that three genes (FAM217B, KIAA1614 and RIBC2) that were significantly elevating the promoter methylation levels in UC compared to normal controls. Interestingly, we confirmed that three genes were transcriptionally silenced in UC patient samples by qRT-PCR, suggesting that their silencing is correlated with the promoter hypermethylation. Pathway analyses were performed using GO and KEGG databases with differentially hypermethylated genes in UC. Our results highlight that aberrant hypermethylation was identified in UC patients which can be a potential biomarker for detecting UC. Moreover, pathway-enriched hypermethylated genes are possibly implicating important cellular function in the pathogenesis of UC. Overall, this study describes a newly hypermethylated gene panel in UC patients and provides new clinical information that can be used for the diagnosis and therapeutic treatment of IBD.
authors: Department of Microbiology, Dankook University, Cheonan 31116, Korea. kangk1204@gmail.com.
authors: Keunsoo
authors: K
authors: Kang
authors: Research Center, Dongnam Institute of Radiological & Medical Sciences (DIRAMS), Busan 46033, Korea. 82jinhan@pusan.ac.kr.
authors: Jin-Han
authors: JH
authors: Bae
authors: Department of Nanobiomedical Science Global Research Center for Regenerative Medicine, Dankook University, Cheonan 31116, Korea. kyudong.han@gmail.com.|DKU-Theragen Institute for NGS Analysis (DTiNa), Dankook University; Cheonan 31116, Korea. kyudong.han@gmail.com.
authors: Kyudong
authors: K
authors: Han
authors: Division of Gastroenterology, Department of Internal Medicine, Kyungpook National University School of Medicine, Daegu 41931, Korea. dandy813@hanmail.net.
authors: Eun Soo
authors: ES
authors: Kim
authors: Department of Internal Medicine, Haeundae Paik Hospital, Inje University College of Medicine, Busan 48108, Korea. kto0440@paik.ac.kr.
authors: Tae-Oh
authors: TO
authors: Kim
authors: Research Center, Dongnam Institute of Radiological & Medical Sciences (DIRAMS), Busan 46033, Korea. jmlee76@gmail.com.
authors: Joo Mi
authors: JM
authors: Yi
mesh_terms: D000328:Adult; D015415:Biomarkers; D003093:Colitis, Ulcerative / Q000235:genetics*; D019175:DNA Methylation / Q000235:genetics*; D044127:Epigenesis, Genetic / Q000235:genetics; D006801:Humans; D066298:In Vitro Techniques; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic / Q000235:genetics
chemical_list: D015415:Biomarkers
keywords: DNA methylation profile; biomarker; promoter hypermethylation; ulcerative colitis