Genetska in farmakogenetska analiza genov iz družine dejavnika tumorske nekroze pri revmatoidnem artritisu

diplomsko delo visokošolskega strokovnega študijskega programa I. stopnje

Danijela Cole (Author), Uroš Potočnik (Mentor), Iztok Holc (Co-mentor), Katja Repnik (Co-mentor)

Abstract

Revmatoidni artritis (v nadaljevanju RA) je avtoimunska bolezen, ki jo povzročajo različni dejavniki. Prizadene približno 1% odraslih v Sloveniji in po svetu, najpogostejše med njimi so ženske. Gre za heterogeno, kronično vnetno bolezen, katera napade sklepe oz. sinovinalno tkivo. Bolezen je posledica delovanja tako okoljskih kot genetskih dejavnikov. Za zdravljenje so najbolj učinkovita biološka zdravila, večina deluje na principu zaviranja dejavnika tumorske nekroze (TNF). Namen naše diplomske naloge je bil poiskati povezave med izbranimi polimorfizmi v genih iz družine TNF in nastankom RA ter odgovor na terapijo pri RA. V nalogi smo se osredotočili na slovensko populacijo, na voljo smo imeli 276 vzorcev bolnikov z RA ter 123 zdravih posameznikov, na katerih smo z metodo verižne reakcije s polimerazo, ki ji je sledil polimorfizem dolžin restrikcijskih fragmentov (PCR-RFLP), ter analizo taljenja visoke ločljivosti (HRM) genotipizirali izbrane polimorfizme posameznega nukleotida (SNP-je) v genu TRAF1 (rs3761847) ter v regiji gena TNFAIP3 (rs6920220). Nadalje smo primerjali alelne in genotipske frekvence analiziranih SNP-jev med bolniki z RA ter zdravimi posamezniki ter glede na klinične podatke. V okviru diplomske naloge smo potrdili statistično značilno povezavo SNP-ja rs6920220 z nastankom RA ter povezavo tega SNP-ja z odgovorom na terapijo, pri čemer je alel A tisti, ki je povišan v skupini bolnikov v primerjavi z zdravimi posamezniki ter je povezan s slabšim odgovorom. Prav tako smo nakazali na morebitno vlogo SNP-ja rs3761847 v genu TRAF1 pri nastanku RA. Tako smo v okviru dela potrdili povezavo genov iz družine dejavnika tumorske nekroze z nastankom in potekom RA v slovenski populaciji ter s tem prispevali nov potencialni biooznačevalec nastanka in poteka RA v slovenski populaciji.

Keywords

revmatoidni artritis;faktor tumorske nekroze;genetika RA;farmakogenetska analiza;diplomske naloge;

Data

Language:	Slovenian
Year of publishing:	2019
Typology:	2.11 - Undergraduate Thesis
Organization:	UM FKKT - Faculty of Chemistry and Chemical Engineering
Publisher:	[D. Cole]
UDC:	575.113:616.72-002.77(043.2)
COBISS:	22690070
Views:	579
Downloads:	62
Average score:	0 (0 votes)
Metadata:

Other data

Secondary language:	English
Secondary title:	Genetic and pharmacogenetic analysis of tumor necrosis factor genes in rheumatoid arthritis
Secondary abstract:	Rheumatoid arthritis (RA) is an autoimmune disease caused by various factors. About 1% of adults in Slovenia and around the world are affected, most often women. It is a heterogeneous, chronic inflammatory disease that attacks the joints specifically synovial tissue. The onset of disease is associated with environmental as well as genetic factors. Biological drugs are one of the most effective treatment for RA and most of these substances act on the principle of inhibiting the function of tumor necrosis factor alpha (TNF-α). The purpose of our thesis was to find associations between selected polymorphisms in TNF genes and the onset of RA and response to RA therapy. We focused on the Slovenian population, 276 samples of RA patients and 123 healthy individuals were available. We genotyped selected polymorphisms in the TRAF1 gene (rs3761847) and in the TNFAIP3 gene (rs6920220) using polymerase chain reaction followed by restriction fragment length polymorphism (PCR-RFLP) and high resolution melting analysis (HRM). We further compared the allele and genotype frequencies of the analyzed SNPs between RA patients and healthy individuals, and according to clinical data. We found statistically significant association between SNP rs6920220 and RA and also with the response to treatment, with A allele as risk allele. We also pointed out the possible role of SNP rs3761847 in gene TRAF1 in RA. We showed that there is association between genes from the family of the tumor necrosis factor and RA in Slovenian population.
Secondary keywords:	rheumatoid arthritis;tumor necrosis factor;genetics of RA;pharmacogenetic analysis;SNP;
Type (COBISS):	Bachelor thesis/paper
Thesis comment:	Univ. v Mariboru, Fak. za kemijo in kemijsko tehnologijo
Pages:	XII, 35 str.
ID:	11227429