Inflammatory bowel disease (IBD) is a composite classification for a range of gastrointestinal disorders. The two most common forms of IBD are Crohn’s disease (CD) and ulcerative colitis (UC). The chronicity of IBD has long-term consequences on the quality of life of affected individuals. However, therapies available today are applied with limited success. It is thought that interplay between environmental triggers and commensal bacteria can cause a dysregulated inflammatory response in genetically predisposed individuals, but the exact etiology is not understood. The objective of these studies was to identify the gene expression changes which associate with differential response to therapy and with recurrence of disease following surgery. The effects of genetic variation on gene expression were also evaluated.
Tissue and blood samples were collected from eligible patients. Total RNA was extracted and measured on gene expression microarrays. The raw gene expression data were analyzed in a statistical framework against variables of interest in order to assess the significance of each association. Genes were evaluated individually as well as in biological networks.
A few tens of genes were identified as differentially expressed in blood between UC patients who respond to intravenous corticosteroid therapy and those who do not. Some of these genes were also shown to have high predictive value. Differentially regulated genes were also found in UC patients who experience recurrence of disease after surgery, relative to those who remain disease-free. Specifically, gene networks responsible for the regulation of cellular transport were among the major players. A comparative analysis of genotype and gene expression in the human ileum indicated that the transcription of approximately 10% of genes is influenced by variations in the genome.
Results from these studies have not only contributed to our understanding of disease mechanism, but could also have medical implications. With the advance of new and less costly transcriptome technologies on the clinical stage, panels of expression markers associated with therapy response and post-operative recurrence can be used as diagnostic and prognostic tools. Data on the relationship between genotype and gene expression are already shedding new light on the function of certain genetic IBD risk variants.
| Identifer | oai:union.ndltd.org:TORONTO/oai:tspace.library.utoronto.ca:1807/43610 |
| Date | 10 January 2014 |
| Creators | Kabakchiev, Boyko |
| Contributors | Silverberg, Mark |
| Source Sets | University of Toronto |
| Language | en_ca |
| Detected Language | English |
| Type | Thesis, Dataset, Software |
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