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Open AccessArticle

A Genome-Wide Methylation Approach Identifies a New Hypermethylated Gene Panel in Ulcerative Colitis

Department of Microbiology, Dankook University, Cheonan 31116, Korea
Research Center, Dongnam Institute of Radiological & Medical Sciences (DIRAMS), Busan 46033, Korea
Department of Nanobiomedical Science Global Research Center for Regenerative Medicine, Dankook University, Cheonan 31116, Korea
DKU-Theragen Institute for NGS Analysis (DTiNa), Dankook University; Cheonan 31116, Korea
Division of Gastroenterology, Department of Internal Medicine, Kyungpook National University School of Medicine, Daegu 41931, Korea
Department of Internal Medicine, Haeundae Paik Hospital, Inje University College of Medicine, Busan 48108, Korea
Authors to whom correspondence should be addressed.
Academic Editor: Alfredo Ciccodicola
Int. J. Mol. Sci. 2016, 17(8), 1291;
Received: 21 June 2016 / Revised: 26 July 2016 / Accepted: 3 August 2016 / Published: 9 August 2016
(This article belongs to the Section Biochemistry)
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. View Full-Text
Keywords: DNA methylation profile; promoter hypermethylation; ulcerative colitis; biomarker DNA methylation profile; promoter hypermethylation; ulcerative colitis; biomarker
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Kang, K.; Bae, J.-H.; Han, K.; Kim, E.S.; Kim, T.-O.; Yi, J.M. A Genome-Wide Methylation Approach Identifies a New Hypermethylated Gene Panel in Ulcerative Colitis. Int. J. Mol. Sci. 2016, 17, 1291.

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