(magistrsko delo)
Tadej Zorjan (Author), Uroš Potočnik (Mentor)

Abstract

Astma je ena najpogostejših kroničnih bolezni dihal v zadnjih desetletjih, saj prizadene okrog deset odstotkov ljudi. V Sloveniji za astmo zboli približno 5 % odraslih in 10 % otrok. Na njen razvoj vplivata tako okolje, kot genetska zasnova posameznikov. V številnih študijah so z astmo povezovali že več kot 600 genov, prispevek vsakega izmed njih pa je verjetno majhen. Mnogi geni, ki bi lahko imeli pomemben vpliv v patogenezi astme še niso poznani oz. si študije o njihovi vlogi na nastanek in fenotip med sabo nasprotujejo. Kandidatni geni se razlikujejo tudi med populacijami. Genetsko ozadje še kljub mnogim raziskavam ni razjasnjeno, saj gre za več-gensko bolezen. Raziskovalci skušajo astmo genetsko opredeliti s študijami na velikih vzorcih in s potrjevanjem rezultatov predhodnih raziskav. Namen magistrskega dela je bil s pomočjo orodij bioinformatike izbrati polimorfizme posameznega nukleotida (SNP) kandidatnih genov za astmo ter z meta-statistično analizo predhodnih študij ugotoviti, kakšna je njihova vloga. Prav tako smo izbrane SNP-e analizirali pri slovenski populaciji. Genotipizirali smo 288 otrok z astmo, od tega 84 z neatopijsko in 189 z atopijsko obliko astme ter 186 zdravih posameznikov kot kontrolno skupino. Ugotovili smo, da je razvoj otroške astme povezan s polimorfizmoma na genih CTLA4 in SLC22A5 in sicer je v skupini bolnikov značilno višja frekvenca genotipov AA (15,1 %) za SNP na genu CTLA4 v primerjavi s kontrolno skupino (24 %; p = 0,027) in prav tako pa je tudi v skupini astmatikov višji delež homozigotov za G (56,5 %) kot v skupini zdravih (55,2 %). Vpliva polimorfizmov na genih IL4, IL4R, NR1/2 in PTGER4 na razvoj astme v slovenski populaciji nismo potrdili, ugotovili pa smo vpliv le teh na potek bolezni, kar se kaže v statistično značilnih razlikah v kliničnih parametrih med bolniki z različnimi genotipi. Z meta-statistično analizo kandidatnih genov pa smo dobili statistično značilne razlike med obema skupinama pri treh polimorfizmih in sicer CCR5_del32 (p = 0,003), CTLA4_+49AG (p = 0,009) in IL4_C+33T (p = 0,02). Ti podatki lahko v bodoče pomembno prispevajo k razumevanju patogeneze astme, ugotovitve o povezavi polimorfizmov z odzivom na terapijo pa lahko vodijo do diagnostične in terapevtske obravnave, ki bo ukrojena po meri vsakega posameznega bolnika z astmo, ter zato veliko učinkovitejša, hitrejša in z manj stranskimi učinki.

Keywords

astma;asociacijska študija;meta-statistična analiza;genska tipizacija;polimorfizem posameznega nukleotida;

Data

Language: Slovenian
Year of publishing:
Source: Maribor
Typology: 2.09 - Master's Thesis
Organization: UM FZV - Faculty of Health Sciences
Publisher: [T. Zorjan]
UDC: 575
COBISS: 1904804 Link will open in a new window
Views: 2403
Downloads: 179
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Other data

Secondary language: English
Secondary title: POLYMORPHISMS OF SELECTED CANDIDATE GENES FOR ASTHMA: META-ANALYSIS OF GENETIC ASSOCIATION STUDIES
Secondary abstract: Asthma is one of the most common chronic diseases of the respiratory system in recent decades, as it affects about ten percent of the people. In Slovenia there are about 5% of adults and 10% of children diagnosed with asthma. Its development is influenced by both the environment as well as the genetic material of individuals. In a number of studies there have already been more than 600 genes associated with asthma; however the contribution of each of them is likely to be small. Many genes, which could have a significant impact in the pathogenesis of asthma, are not yet known or the studies on their impact in the formation and the phenotype differ. The candidate genes differ between populations as well. The genetic background has yet, despite a lot of research, not been resolved yet, due to the fact that it is a multi-GM disease. Researchers are trying to identify it by genetic studies on large samples and validation of previous research. The purpose of the master's work was to select specific bioinformatics nucleotide polymorphisms (SNP) of candidate genes for asthma and to determine their role through a meta-statistical-analysis of previous studies. We have also analyzed the selected SNP-e with the Slovenian population. We have determined 288 genes of children with asthma, of which 84 with non-atopic and 189 with atopic form of asthma and 186 healthy individuals as a control group. We have found that the development of children's asthma is associated with polymorphisms on the genes and CTLA4 SLC22A5 as a higher frequency of genotypes AA (15,1%) for the SNP to CTLA4 gene in a group of patients was characterized compared to the control group (24%; p = 0,027), and also in the group there was a higher share of allele homozygote asthmatics G (56,5 %) than in the healthy group (55,2 %). We haven't confirmed the impact of polymorphisms in IL4, IL4R genes, NR1/2 and PTGER4 on the development of asthma in the population, but we found the impact of these on the course of the disease, which results in statistically significant differences in the clinical parameters between patients with different genotypes. Due to the meta-analysis of the candidate genes statistically, however, we got a significant difference between the two groups of three polymorphisms, namely CCR5_del32 (p = 0,003), and CTLA4 _ + 49AG (p = 0,009) and IL4_C + 33T (p = 0,02). These data may in the future contribute significantly to the understanding of the pathogenesis of asthma, findings about the connection with response to therapy and polymorphisms may lead to diagnostic and therapeutic treatment of it, which will be tailed according to each asthma patient individually, and therefore the treatment will be much more efficient, faster and with fewer side effects.
Secondary keywords: asthma;association studies;meta-statistical analysis;genetic typification;single nucleotide polymorphism;
URN: URN:SI:UM:
Type (COBISS): Master's thesis/paper
Thesis comment: Univ. v Mariboru, Fak. za zdravstvene vede
Pages: XIX, 158 str.
Keywords (UDC): mathematics;natural sciences;naravoslovne vede;matematika;biological sciences in general;biologija;general genetics;general cytogenetics;splošna genetika;splošna citogenetika;
ID: 16305