Year: 2013
Type: dissertation
Study design: Observational Study
Abstract: The etiology of ulcerative colitis (UC), a chronic inflammatory bowel disease, is still not fully understood. One of the current hypotheses is, that genetic and environmental factors modulate the epigenetic landscape and thus contribute to susceptibility, manifestation and progression of the disease. In the presented thesis, a three-layer epigenome-wide association study (EWAS) is reported, using intestinal biopsies from ten monozygotic twin pairs discordant for the manifestation of UC (n=20). The primary result is a map of links between disease-associated transcripts and epigenetic modifications. These candidates of cis-linked gene expression and DNA methylation (DNAm) were validated in two larger independent patient populations (n=185) by quantitative real-time PCR and bisulfite-pyrosequencing, resulting high DNAm/RNA correlations, indicating a potential impact of DNAm on transcription. Many of the identified candidate genes have been functionally implicated in inflammatory processes. In contrast to the observed hypomethylation of several candidate loci in UC, patients with acute inflammation showed no altered methylation. To validate an alternative epigenetic modification in these patients, hydroxymethylation was quantified at selected loci, indicating that this mechanism might play a role in acute inflammation when compared to chronic inflammation. In conclusion, this study represents the first replicated EWAS in affected tissue of UC patients, integrated with transcriptional signatures. The results indicate a potential role of epigenetic modification in disease manifestation and progression of UC.
Author: Zhe Feng
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2545338373