Polimorfizam nukleotida rs531564 gena za pri-miR-124 u bolesnika s primarnim sklerozirajućim kolangitisom i upalnom bolesti crijeva

doctoral thesis

• Title (english): Nucelotide polymorphism rs531564 of pri-miR-124 gene in patients with primary sclerosing cholangitis and inflammatory bowel disease
• Author: Mislav Jelaković
• Mentor: Silvija Čuković-Čavka (mentor)
• Committee member: Neven Ljubičić (predsjednik povjerenstva)
• Committee member: Željko Krznarić (član povjerenstva)
• Committee member: Tamara Nikuševa Martić (član povjerenstva)
• Granter: University of Zagreb; School of Medicine; (Department of Internal Medicine); Zagreb
• Defense date and country: 2025-03-21, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Clinical Medical Sciences; Internal Medicine
• Universal decimal classification (UDC): 616 - Pathology. Clinical medicine

Abstract

Upalne bolesti crijeva (UBC) kronične su imunosno posredovane bolesti genski predisponiranih osoba, čija etiopatogeneza nije potpuno razjašnjena. Posebno se ističe fenotip UBC-a kod pacijenata s primarnim sklerozirajućim kolangitisom (PSC). UK i CB u tih bolesnika dominantno zahvaćaju kolon, karakteristično su blažeg tijeka, ali uz povišen rizik razvoja kolorektalnog karcinoma, a i drugih malignih bolesti. Rezultati naše kohorte bolesnika su u skladu s dosad publiciranim podacima u literaturi.
Smatra se da miR imaju važnu ulogu u navedenoj patogenezi. Uloga miR-124 posebno je istražena, pokazujući važnost u održavanju integriteta crijevne barijere i regulaciji proinflamatornih citokina, a SNP (rs531564) gena povezan je s njezinom ekspresijom.
Cilj ovog ispitivanja bio je prvi put u ovoj populaciji analizirati učestalost genotipa navedenog SNP-a.
Nismo uspjeli pokazati značajne razlike u genotipu između ispitivane (UBC/PSC) i kontrolne skupine (UBC). Genotip GG numerički je učestaliji u bolesnika s UBC-om u odnosu na PSC, ali razlike nisu bile statistički značajne. Nije pronađena značajna razlika po genotipu za kliničke ili demografske varijable osim za bolesnike s UK-om, gdje su ispitanici s genotipom GC bili značajno mlađi te su mlađi započinjali biološku terapiju u odnosu na ispitanike s genotipom GG. Potrebna su daljnja, multicentrična istraživanja na većem uzorku kako bi se potvrdili ovi nalazi.

Abstract (english)

Inflammatory bowel diseases (IBD) are chronic, immunologically mediated diseases of genetically predisposed individuals, whose etiopathogenesis is not fully understood. The phenotype of IBD in patients with primary sclerosing cholangitis (PSC) is particularly notable. Ulcerative colitis (UC) and Crohn's disease (CD) in these patients predominantly affect the colon and are characteristically milder in course but with an increased risk of developing colorectal cancer as well as other malignancies. The results from our cohort of patients are consistent with previously published data in the literature.
It is believed that microRNAs (miRNAs) play an important role in the aforementioned pathogenesis. The role of miR-124 has been particularly studied, showing its importance in maintaining intestinal barrier integrity and regulating pro-inflammatory cytokines, with the SNP (rs531564) gene being associated with its expression.
The aim of this study was to analyze, for the first time in this population, the frequency of genotypes of the mentioned SNP.
We did not show significant differences in genotype between the study group (IBD/PSC) and the control group (IBD). The GG genotype was numerically more prevalent in patients with IBD compared to PSC, but the differences were not statistically significant. No significant difference was found by genotype for clinical or demographic variables except for UC patients, where participants with the GC genotype were significantly younger and started biological therapy earlier compared to the GG genotype. Further multicentric studies on larger samples are needed to confirm these findings.

• Keywords: Kolitis; ulcerozni; Citokini; Kolangitis; Upalne bolesti crijeva; Crohnova bolest; MikroRNA; Fenotip; Genotip
• Keywords (english): Colitis; Ulcerative; Cytokines; Cholangitis; Inflammatory Bowel Diseases; Crohn Disease; MicroRNAs; Phenotype; Genotype
• Language: croatian
• URN:NBN: urn:nbn:hr:105:595524
• Study programme: Title: Biomedicine and Health Sciences; Study programme type: university; Study level: postgraduate; Academic / professional title: doktor/doktorica znanosti, područje biomedicine i zdravstvo (doktor/doktorica znanosti, područje biomedicine i zdravstvo)
• Type of resource: Text
• Extent: 78 str.
• File origin: Born digital
• Access conditions: Open access
• Created on: 2025-03-27 09:01:09