Whole genome gene expression meta-analysis of inflammatory bowel disease colon mucosa demonstrates lack of major differences between Crohn's disease and ulcerative colitis

• Published in: PloS one Vol. 8; no. 2; p. e56818
• Main Authors: Granlund, Atle van Beelen, Flatberg, Arnar, Østvik, Ann E, Drozdov, Ignat, Gustafsson, Bjørn I, Kidd, Mark, Beisvag, Vidar, Torp, Sverre H, Waldum, Helge L, Martinsen, Tom Christian, Damås, Jan Kristian, Espevik, Terje, Sandvik, Arne K
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 13.02.2013; Public Library of Science (PLoS)
• Subjects: Adult; Aged; Analysis; Antimicrobial Cationic Peptides - genetics; Archives & records; Biology; Cancer; Cell adhesion & migration; Cell differentiation; Cluster Analysis; Colitis; Colitis, Ulcerative - genetics; Colitis, Ulcerative - immunology; Colon; Colon - immunology; Colon - metabolism; Crohn Disease - genetics; Crohn Disease - immunology; Crohn's disease; Crohns disease; Cytokines; Data processing; Differentiation (biology); Disease susceptibility; DNA microarrays; Environmental factors; Female; Gastroenterology; Gastrointestinal diseases; Gene expression; Gene Expression Profiling; Gene Expression Regulation; Genes; Genetic aspects; Genome, Human; Genomes; Genomics; Helper cells; Hepatology; Homeostasis; Hospitals; Humans; Inflammation; Inflammatory bowel disease; Inflammatory bowel diseases; Inflammatory Bowel Diseases - genetics; Inflammatory Bowel Diseases - immunology; Intestinal Mucosa - immunology; Intestinal Mucosa - metabolism; Intestine; Lymphocytes T; Male; Mathematical models; Medical research; Medicine; Meta-analysis; Middle Aged; Molecular biology; Mucosa; Patients; Proteins; Science; Statistical methods; Studies; T-Lymphocytes, Helper-Inducer - immunology; T-Lymphocytes, Helper-Inducer - metabolism; Ulcerative colitis; Young Adult; Norway
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0056818

In inflammatory bowel disease (IBD), genetic susceptibility together with environmental factors disturbs gut homeostasis producing chronic inflammation. The two main IBD subtypes are Ulcerative colitis (UC) and Crohn's disease (CD). We present the to-date largest microarray gene expression study on IBD encompassing both inflamed and un-inflamed colonic tissue. A meta-analysis including all available, comparable data was used to explore important aspects of IBD inflammation, thereby validating consistent gene expression patterns. Colon pinch biopsies from IBD patients were analysed using Illumina whole genome gene expression technology. Differential expression (DE) was identified using LIMMA linear model in the R statistical computing environment. Results were enriched for gene ontology (GO) categories. Sets of genes encoding antimicrobial proteins (AMP) and proteins involved in T helper (Th) cell differentiation were used in the interpretation of the results. All available data sets were analysed using the same methods, and results were compared on a global and focused level as t-scores. Gene expression in inflamed mucosa from UC and CD are remarkably similar. The meta-analysis confirmed this. The patterns of AMP and Th cell-related gene expression were also very similar, except for IL23A which was consistently higher expressed in UC than in CD. Un-inflamed tissue from patients demonstrated minimal differences from healthy controls. There is no difference in the Th subgroup involvement between UC and CD. Th1/Th17 related expression, with little Th2 differentiation, dominated both diseases. The different IL23A expression between UC and CD suggests an IBD subtype specific role. AMPs, previously little studied, are strongly overexpressed in IBD. The presented meta-analysis provides a sound background for further research on IBD pathobiology.