Blood-Derived DNA Methylation Signatures of Crohn's Disease and Severity of Intestinal Inflammation

作者: Hari K. Somineni , Suresh Venkateswaran , Varun Kilaru , Urko M. Marigorta , Angela Mo

DOI: 10.1053/J.GASTRO.2019.01.270

关键词:

摘要: Background & Aims Crohn's disease is a relapsing and remitting inflammatory disorder with variable clinical course. Although most patients present an phenotype (B1), approximately 20% of rapidly progress to complicated disease, which includes stricturing (B2), within 5 years. We analyzed DNA methylation patterns in blood samples pediatric at diagnosis later time points identify changes that associate might contribute development progression. Methods obtained from 164 (1–17 years old) (B1 or B2) who participated North American study were followed for Participants without intestinal inflammation symptoms served as controls (n = 74). collected 1–3 850,000 sites. used genetic association the concept Mendelian randomization result disease. Results identified 1189 5′-cytosine–phosphate–guanosine-3′ (CpG) sites differentially methylated between (at diagnosis) controls. Methylation these correlated plasma levels C-reactive protein. A comparison profiles vs during follow-up period showed that, treatment, alterations more closely resembled observed controls, irrespective progression B2. 3 CpG Most associated disappeared treatment be Conclusions accompany acute inflammation; change resemble inflammation. These findings indicate disease–associated are features less likely

参考文章(45)
Mohan S. Maddur, Pierre Miossec, Srini V. Kaveri, Jagadeesh Bayry, Th17 Cells: Biology, Pathogenesis of Autoimmune and Inflammatory Diseases, and Therapeutic Strategies American Journal of Pathology. ,vol. 181, pp. 8- 18 ,(2012) , 10.1016/J.AJPATH.2012.03.044
S Liu, J. Z., van Sommeren, S., Huang, H., Ng, S. C., Alberts, R., Takahashi, A., ... & Abedian, Association analyses identify 38 susceptibility loci for inflammatory bowel disease and highlight shared genetic risk across populations Nature Genetics. ,vol. 47, pp. 979- 986 ,(2015) , 10.1038/NG.3359
Joannie Ruel, Darren Ruane, Saurabh Mehandru, Corinne Gower-Rousseau, Jean-Frédéric Colombel, IBD across the age spectrum: is it the same disease? Nature Reviews Gastroenterology & Hepatology. ,vol. 11, pp. 88- 98 ,(2014) , 10.1038/NRGASTRO.2013.240
Xiang Zhou, Matthew Stephens, Genome-wide efficient mixed-model analysis for association studies Nature Genetics. ,vol. 44, pp. 821- 824 ,(2012) , 10.1038/NG.2310
R Alan Harris, Dorottya Nagy-Szakal, Sabina AV Mir, Eibe Frank, Reka Szigeti, Jess L Kaplan, Jiri Bronsky, Antone Opekun, George D Ferry, Harland Winter, Richard Kellermayer, DNA methylation-associated colonic mucosal immune and defense responses in treatment-naïve pediatric ulcerative colitis. Epigenetics. ,vol. 9, pp. 1131- 1137 ,(2014) , 10.4161/EPI.29446
Elaine R. Nimmo, James G. Prendergast, Marian C. Aldhous, Nicholas A. Kennedy, Paul Henderson, Hazel E. Drummond, Bernard H. Ramsahoye, David C. Wilson, Colin A. Semple, Jack Satsangi, Genome-wide methylation profiling in Crohn's disease identifies altered epigenetic regulation of key host defense mechanisms including the Th17 pathway. Inflammatory Bowel Diseases. ,vol. 18, pp. 889- 899 ,(2012) , 10.1002/IBD.21912
Atle van Beelen Granlund, Arnar Flatberg, Ann E. Østvik, Ignat Drozdov, Bjørn I. Gustafsson, Mark Kidd, Vidar Beisvag, Sverre H. Torp, Helge L. Waldum, Tom Christian Martinsen, Jan Kristian Damås, Terje Espevik, Arne K. Sandvik, Whole Genome Gene Expression Meta-Analysis of Inflammatory Bowel Disease Colon Mucosa Demonstrates Lack of Major Differences between Crohn's Disease and Ulcerative Colitis PLoS ONE. ,vol. 8, pp. e56818- ,(2013) , 10.1371/JOURNAL.PONE.0056818
Kyle Kai-How Farh, Alexander Marson, Jiang Zhu, Markus Kleinewietfeld, William J Housley, Samantha Beik, Noam Shoresh, Holly Whitton, Russell JH Ryan, Alexander A Shishkin, Meital Hatan, Marlene J Carrasco-Alfonso, Dita Mayer, C John Luckey, Nikolaos A Patsopoulos, Philip L De Jager, Vijay K Kuchroo, Charles B Epstein, Mark J Daly, David A Hafler, Bradley E Bernstein, None, Genetic and epigenetic fine mapping of causal autoimmune disease variants Nature. ,vol. 518, pp. 337- 343 ,(2015) , 10.1038/NATURE13835
Anaïs Peneau, Guillaume Savoye, Dominique Turck, Luc Dauchet, Mathurin Fumery, Julia Salleron, Eric Lerebours, Karine Ligier, Francis Vasseur, Jean-Louis Dupas, Olivier Mouterde, Claire Spyckerelle, Djamal Djeddi, Laurent Peyrin-Biroulet, Jean-Frédéric Colombel, Corinne Gower-Rousseau, Mortality and Cancer in Pediatric-Onset Inflammatory Bowel Disease: A Population-Based Study The American Journal of Gastroenterology. ,vol. 108, pp. 1647- 1653 ,(2013) , 10.1038/AJG.2013.242
Tibor Krenács, Katalin Leiszter, Tamás Zágoni, Györgyi Muzes, Zsolt Tulassay, Ferenc Sipos, Orsolya Galamb, Barnabás Wichmann, Kinga Tóth, Béla Molnár, Peripheral Blood Based Discrimination of Ulcerative Colitis and Crohn’s Disease from Non-IBD Colitis by Genome-Wide Gene Expression Profiling Disease Markers. ,vol. 30, pp. 1- 17 ,(2011) , 10.3233/DMA-2011-0758