Uloga CpG metilacije gliko-gena MGAT3 i MGAT5 te glikozilacije imunoglobulina G u upalnim bolestima crijeva

doctoral thesis

• Title (english): CpG methylation of MGAT3 and MGAT5 glyco-genes and glycosylation of immunoglobulin G in inflammatory bowel diseases
• Author: Dora Markulin
• Mentor: Vlatka Zoldoš (mentor)
• Committee member: Petra Korać (član povjerenstva)
• Committee member: Ivana Ivančić Baće (član povjerenstva)
• Committee member: Gordan Lauc (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Biology); Zagreb
• Defense date and country: 2017, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Biology
• Universal decimal classification (UDC): 57 - Biological sciences. Physical anthropology. Biodiversity

Abstract

Upalne bolesti crijeva (engl. inflammatory bowel diseases, IBD) su kronične bolesti probavnog trakta koje nastaju zbog neodgovarajućeg upalnog odgovora imunološkog sustava na crijevnu mikrofloru u osoba s genetičkom predispozicijom. Cjelogenomske studije povezanosti su povezale gliko-gen MGAT3 s glikozilacijom imunoglobulina G (IgG) i IBD-em. Druga istraživanja su s razvojem IBD-a povezala i gliko-gen MGAT5. Bisulfitnim pirosekvenciranjem analizirala sam metilaciju gena MGAT3 i MGAT5 iz krvi pacijenata s IBD-em dviju velikih neovisnih kohorti te pokazala da je metilacija ovih gena značajno promijenjena u ulceroznom kolitisu i Crohnovoj bolesti. Korelacijske analize upućuju na smanjenu ekspresiju gena MGAT3 (kodira za enzim GnT-III) u IBD-u, ako je točna pretpostavka da su analizirana CpG mjesta unutar promotora tog gena uključena u regulaciju ekspresije. U trećoj manjoj kohorti analizirala sam metilaciju gena MGAT3 i MGAT5 u mononuklearnim stanicama krvi, T-limfocitima izoliranim iz krvi i iz tkiva crijeva, te pokazala značajnu promjenu metilacije oba gena u T-limfocitima iz crijeva, te promijenjenu metilaciju i ekspresiju gena MGAT5 u T-limfocitima iz tkiva crijeva pacijenata s aktivnim oblikom ulceroznog kolitisa.

Abstract (english)

Inflammatory bowel diseases (IBD) are a group of intestinal disorders that occur due to inappropriate immune response to intestinal microbiome in genetically susceptible individuals. Genome wide association studies associated MGAT3 gene with IgG glycosylation and IBD. Previous studies associated another glyco-gene, MGAT5 with IBD, too. Methylation of MGAT3 and MGAT5 genes was analysed from whole blood of IBD patients from two large independent cohorts using bisulfite pyrosequencing. The results showed significant change in methylation level between patients with Crohn's disease and ulcerative colitis, and healthy controls. Correlation analysis between MGAT3 methylation and IgG glycans suggests that MGAT3 (coding for GnT-III enzyme) expression is reduced in IBD, if CpG sites encompassed with methylation assays are relevant for transcriptional regulation. In third cohort with smaller number of patients with ulcerative colitis, methylation of MGAT3 and MGAT5 genes was analysed in mononuclear cells from blood, T cells from blood, and T cells from inflamed bowel tissue. Change in methylation level of both genes was observed only in T cells from bowel tissue. The methylation and expression of MGAT5 gene was significantly changed in T cells from bowel tissue in active ulcerative colitis.

• Keywords: Crohnova bolest; ulcerozni kolitis; metilacija DNA; MGAT3; MGAT5; N-glikozilacija; imunoglobulin G
• Keywords (english): Crohn's disease; ulcerative colitis; DNA methylation; MGAT3; MGAT5; N-glycosylation; immunoglobulin G
• Language: croatian
• URN:NBN: urn:nbn:hr:217:286867
• Study programme: Title: Biology; Study programme type: university; Study level: postgraduate; Academic / professional title: doktor/doktorica znanosti, područje prirodnih znanosti, polje biologija (doktor/doktorica znanosti, područje prirodnih znanosti, polje biologija)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access; Embargo expiration date: 2019-05-25
• Created on: 2017-06-06 12:04:53