Elevation in cell cycle and protein metabolism gene transcription in inactive colonic tissue from Icelandic patients with ulcerative colitis
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PROVIDER: PRJNA414600 | ENA |
REPOSITORIES: ENA
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Project description:BACKGROUND & AIMS: Ulcerative colitis (UC) is a chronic relapsing inflammatory disorder that affects the colonic epithelium. A combination of genetic and environmental factors is thought to be involved in the pathogenesis, resulting in an abnormal immune response and destruction of the colonic epithelium. In Iceland, the incidence of UC is one of the highest in the world and is three times more common than Crohn’s disease. Previous studies have suggested a genetic component may have an influence on the increased incidence. The aim of this study was to characterise a cohort of patients with UC and identify potential germ line mutations and pathways which could be associated with UC in this population. METHODS: We performed exome sequencing of genomic DNA and genome-wide microarray analysis on macroscopically non-inflamed colonic mucosa from Icelandic patients with UC and age and sexed matched controls. Gene-ontology analysis was used to identify common processes and pathways differentially expressed in tissue from UC cases. Exome sequence data were examined for very rare or novel mutations which might be over represented in the UC cohort. Combined matching of variant analysis and downstream influence on transcriptomic expression in the rectum was also analysed. RESULTS: Non-inflamed colonic tissue from patients with UC demonstrated a significant alteration in the transcriptomic profile compared to controls. Over 2,000 genes were differentially expressed in rectal tissue from UC patients and gene ontology analysis identified an up-regulation in genes associated with cell cycle control and protein processing in the endoplasmic reticulum. Exome sequencing identified two missense mutations in thiopurine S-methyltransferase (TPMT) with a minor allele frequency of 0.22 in the UC patients compared to a reported 0.062 in the Icelandic population and 0.03 in the non-Finnish European populations. A predicted damaging mutation in the inflammatory bowel disease associated gene SLC26A3 was identified which was associated with increased expression of DUOX2 and DUOXA2 in UC rectal tissue. CONCLUSIONS: In patients with UC, the colonic mucosa demonstrates a clear alteration in gene expression compared to control subjects. There is evidence of an elevation in genes involved with cell proliferation and the processing of proteins within the endoplasmic reticulum. Exome sequencing identified an increased prevalence of two damaging TPMT variants within the Icelandic UC population, which would suggest screening the UC population prior to initiation of therapy is warranted in order to avoid the serious toxicity associated with these mutations and azathioprine treatment.
2018-11-01 | GSE105074 | GEO
Project description:BackgroundA combination of genetic and environmental factors is thought to be involved in the pathogenesis of ulcerative colitis (UC). In Iceland, the incidence of UC is one of the highest in the world. The aim of this study was to characterize patients with UC and identify potential germline mutations and pathways that could be associated with UC in this population.MethodsExome sequencing and genome-wide microarray analysis on macroscopically noninflamed colonic mucosa from patients and controls were performed. Exome sequence data were examined for very rare or novel mutations that were over-represented in the UC cohort. Combined matching of variant analysis and downstream influence on transcriptomic expression in the rectum were analyzed.ResultsOne thousand eight hundred thirty-eight genes were differentially expressed in rectal tissue from UC patients and identified an upregulation in genes associated with cell cycle control and protein processing in the endoplasmic reticulum (ER). Two missense mutations in thiopurine S-methyltransferase (TPMT) with a minor allele frequency of 0.22 in the UC patients compared with a reported 0.062 in the Icelandic population were identified. A predicted damaging mutation in the gene SLC26A3 is potentially associated with increased expression of DUOX2 and DUOXA2 in rectal tissue.ConclusionsColonic mucosa of UC patients demonstrates evidence of an elevation in genes involving cell proliferation and processing of proteins within the ER. Exome sequencing identified a possible increased prevalence of 2 damaging TPMT variants within the UC population, suggesting screening the UC population before initiation of thiopurine analogue therapy to avoid toxicity associated with these mutations.
| S-EPMC6327231 | biostudies-literature
Project description:The samples are a part of a study aiming at diagnosing ulcerative colitis from genome-wide gene expression analysis of the colonic mucosa. Colonic mucosal samples were collected as endoscopic pinch biopsies from ulcerative colitis patients and from control subjects. Samples with and without macroscopic signs of inflammation were collected from the patients. Experiment Overall Design: The series contain eight UC samples with macroscopic signs of inflammation, 13 UC smaples without macroscopic signs of inflammation, five control subjects.
2008-06-20 | E-GEOD-9452 | biostudies-arrayexpress
Project description:Ulcerative colitis is a chronic inflammatory disorder in the lower part of the digestive system. Despite of many functional studies, the hidden mechanisms of this complex disease limit complete remission. Here, we investigated transcriptomic signature of ulcerative colitis using RNA sequencing obtained from 15 active (inflamed), 15 inactive (non-inflamed) samples of ulcerative colitis, and 15 healthy controls. The transcriptomics profiling revealed that inflammatory transcriptomic signature was highly enriched in active samples compared to inactive or healthy control samples. However, this bulk RNAseq cannot provide the cell type information, which play a key role in such a chronic inflammation. To overcome this limitation, we borrowed the power of single cell RNAseq. Deconvolution of bulk RNAseq based on the single cell expression estimated active UC enriched cell types including inflammatory fibroblast and inflammatory monocytes. This integrative approach using bulk and single cell transcriptomics provide not only target genes but also target cell types of ulcerative colitis for therapeutic purpose.
2024-03-19 | GSE243625 | GEO
Project description:Colonoscopy biopsies from patients with ulcerative colitis were collected prior to biological therapy. The sampled mucosa was the area of active lesion. Heterogenety of the samples were studied.
2022-12-17 | GSE220815 | GEO
Project description:Ulcerative colitis related gene expressions analysis in colonic biopsy samples from control and ulcerative colitis patients
2019-07-10 | GSE134025 | GEO
Project description:The series was designed to identify the different methylated single CpGs involved in the pathophysiology of ulcerative colitis. A cohort of n=20 monozygotic twins, discordant for ulcerative colitis was selected. Illumina and Nimblegen platforms were used.
2012-09-27 | E-GEOD-27899 | biostudies-arrayexpress
Project description:Expression data was used to evaluate changes to the transcriptional signatures across the healthy and inflamed colon. A comparison between healthy controls and active ulcerative colitis signatures was also made. Mucosal biopsy specimens were harvested at four anatomical locations within the colon from healthy volunteers and patients with active ulcerative colitis. specimens were fixed in RNA later for 24 hours at room temperature and stored at -80C for a further 24 hours prior to RNA extraction and microarray analysis.
2015-01-21 | E-GEOD-65114 | biostudies-arrayexpress
Project description:To assess mRNA gene expression levels in patients with ulcerative colitis (UC) and healthy controls.
2024-07-01 | GSE206171 | GEO