diplomsko delo univerzitetnega študijskega programa I. stopnje
Povzetek
Kronična vnetna črevesna bolezen (KVČB) je dolgotrajno (kronično) obolenje črevesja, ki je imunsko pogojeno. Med KVČB uvrčamo dve bolezni, ki sta si precej podobni, to sta Crohnova bolezen (CB) in ulcerozni kolitis (UK), v 10-15% pa bolezni ne moremo razvrstiti v prejšnji skupini, zato jo uvrščamo v intermediarni kolitis (KI) [1]. Vzroki za KVČB še niso dodobra pojasnjeni, vendar pa so odvisni od okoljskih in genetskih dejavnikov. KVČB uvrščamo med kompleksne kronične imunske bolezni, med katere sodijo tudi nekatera druga obolenja, kot so revmatoidni artritis, multipla skleroza itd. Bolezen KVČB zdravijo na več načinov, v današnjih časih pa dajejo velik poudarek na biološka zdravila, ki so večinoma zelo učinkovita, vendar pa pri nekaterih pacientih opažamo neodzivnost.
V diplomskem delu smo se lotili analize ekspresijskih in epigenetskih profilov pri slovenskih bolnikih s kronično vnetno črevesno boleznijo na anti-TNF terapiji z adalimumabom (ADA). Cilj je bila identifikacija kandidatnih biooznačevalcev, ki bi predvideli bolnikovo odzivnost na tovrstno biološko zdravljenje. Odločili smo se za testiranje gena AXIN1. V študiji pri bolnikih z revmatoidnim artritisom, ki je tako kot KVČB kronična vnetna avtoimuna bolezen, je bila namreč dokazana različna stopnja metiliranosti tega gena pri odzivnikih in neodzivnikih na adalimumab [2]. Tako kot pri KVČB, tudi pri RA uporabljajo biološke terapije in pri obeh je približno 20-40 % neodzivnikov na tako terapijo [3], [4].
Ugotovili smo, da je pri bolnikih s KVČB statistično značilno povečanje izražanje gena za AXIN1 v primerjavi z zdravimi kontrolami, vendar je razlika zelo majhna, med odzivniki in neodzivnki pa ni bilo opaziti razlik. Za namen epigenetskih študij smo pripravili različne metilacijske kontrole in poskusili optimizirati metilacijske teste. Ker naše epigenetske analize niso dale jasnih končnih rezultatov, bodo potrebne nadaljnje preiskave.
Ključne besede
odzivniki;neodzivniki;genska ekspresija;diplomske naloge;
Podatki
Jezik: |
Slovenski jezik |
Leto izida: |
2018 |
Tipologija: |
2.11 - Diplomsko delo |
Organizacija: |
UM FKKT - Fakulteta za kemijo in kemijsko tehnologijo |
Založnik: |
[I. Kelc] |
UDK: |
615.246:616.34-009(043.2) |
COBISS: |
21415958
|
Št. ogledov: |
1468 |
Št. prenosov: |
109 |
Ocena: |
0 (0 glasov) |
Metapodatki: |
|
Ostali podatki
Sekundarni jezik: |
Angleški jezik |
Sekundarni naslov: |
Expression and epigenetic profiles in patients with chronic inflammatory bowel disease |
Sekundarni povzetek: |
Chronic inflammatory bowel disease (IBD) is a long-term (chronic) bowel disease that is immune-dependent. Among the IBD, we classify two diseases that are quite similar, those are Chron's disease (CD) and ulcerative colitis (UC), and in 10-15% of the disease can not be classified in the previous group, so it is classified as indirect colitis (IC) [1]. The causes for IBD are not yet well understood, but they depend on environmental and genetic factors. IBD is classified as complex chronic immune disease, this also includes some other diseases such as rheumatoid arthritis, multiple sclerosis, etc. They cure the disease in several ways, but nowadays there is more focus on biological medicines, which are mostly very effective, but in some pacients we notice unrespond.
In the diploma work we analyzed expression and epigenetic profiles in Slovene patients with chronic inflammatory bowel disease on anti-TNF therapy with adalimumab (ADA). The aim of the study was to identify biological markers that would anticipate the patient's response to this type of biological treatment. We decided to test the AXIN1 gene. In research of methylation in the patients with rheumatoid arthritis was proven to be different rate of methylation in responders and nonresponders on adalimumab [2]. As with IBD, they also use biological therapies for RA, and for both, about 20-40% are unresponders on such therapy [3], [4].
We found that in patients with IBD there was a statistically significant increase in the expression of the AXIN1 gene compared to healthy controls, but the difference was very small, and there were no differences between the responders and the unresponders. For the purpose of epigenetic studies, various methylation controls were prepared and optimized metilation tests were performed. Because our epigenetic analyzes did not give clear final results, further investigations will be needed. |
Sekundarne ključne besede: |
adalimumab;responders;unrespondes;gene expresion;methylation; |
URN: |
URN:SI:UM: |
Vrsta dela (COBISS): |
Diplomsko delo/naloga |
Komentar na gradivo: |
Univ. v Mariboru, Fak. za kemijo in kemijsko tehnologijo |
Strani: |
IX, 36 str. |
ID: |
10925058 |