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Identification of disease-associated DNA methylation in intestinal tissues from patients with inflammatory bowel disease

Authors


Zhenwu Lin, PhD, Department of Surgery, College of Medicine, The Pennsylvania State University, 500 University Drive, H 137, Hershey, PA 17033, USA.
Tel.: +1 717 531 0003x285182;
fax: +1 717 531 0646;
e-mail: zlin@hmc.psu.edu

Walter A Koltun, MD, Department of Surgery, College of Medicine, The Pennsylvania State University, 500 University Drive, H 137, Hershey, PA 17033, USA.
Tel.: +1 717 531 8375;
fax: +1 717 531 0646;
e-mail: wkoltun@hmc.psu.edu

Abstract

Lin Z, Hegarty JP, Cappel JA, Yu W, Chen X, Faber P, Wang Y, Kelly AA, Poritz LS, Peterson BZ, Schreiber S, Fan J-B, Koltun WA. Identification of disease-associated DNA methylation in intestinal tissues from patients with inflammatory bowel disease.

Overwhelming evidence supports the theory that inflammatory bowel disease (IBD) is caused by a complex interplay between genetic predispositions of multiple genes, combined with an abnormal interaction with environmental factors. It is becoming apparent that epigenetic factors can have a significant contribution in the pathogenesis of disease. Changes in the methylation state of IBD-associated genes could significantly alter levels of gene expression, potentially contributing to disease onset and progression. We have explored the role of DNA methylation in IBD pathogenesis. DNA methylation profiles (1505 CpG sites of 807 genes) of matched diseased (n = 26) and non-diseased (n = 26) intestinal tissues from 26 patients with IBD [Crohn's disease (CD) n = 9, ulcerative colitis (UC) n = 17] were profiled using the GoldenGate™ methylation assay. After an initial identification of a panel of 50 differentially methylated CpG sites from a training set (14 non-diseased and 14 diseased tissues) and subsequent validation with a testing set (12 non-diseased and 12 diseased tissues), we identified seven CpG sites that are differentially methylated in intestinal tissues of IBD patients. We have also identified changes in DNA methylation associated with the two major IBD subtypes, CD and UC. This study reports IBD-associated changes in DNA methylation in intestinal tissue, which may be disease subtype-specific.

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