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Vpliv izbranih polimorfizmov v genih SLC22A31, SFTPD, THBS3, NR1H2 in LZTFL1 na potek bolezni covid-19
ID Mazej, Nika (Author), ID Karas Kuželički, Nataša (Mentor) More about this mentor... This link opens in a new window, ID Urbančič, Dunja (Comentor)

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Abstract
Od pojava bolezni leta 2019 je imel covid-19 velik vpliv na svetovno populacijo. Posledično je bil tudi predmet velikega števila raziskav; med drugim so le-te želele ugotoviti, kateri so dejavniki tveganja za razvoj težjega poteka bolezni. Ugotovili so, da imajo velik vpliv genetske spremembe. Polimorfizem rs1405655 v genu NR1H2 je bil na primer v literaturi pokazan kot dejavnik tveganja za pojav hujših nevroloških simptomov in posledično težjega poteka bolezni. Polimorfizem rs721917 v genu SFTPD so povezali z vstopom virusa v gostiteljsko celico preko vezave na receptor za encim angiotenzinske konvertaze 2. Polimorfizem rs117169628 v genu SLC22A31 so povezali z regulacijo transmembranskih proteinov in posledičnim vplivom na vstop virusa skozi membrano. Polimorfizem rs67579710 v genu THBS3 je v literaturi koreliral s pojavom tromboze tekom prebolevanja bolezni. V literaturi so opazili povezavo med polimorfizmom rs71325088 v genu LZTFL1 in vstopom virusa preko pljučnih epitelnih celic. Namen magistrske naloge je bil ugotoviti, ali omenjeni polimorfizmi vplivajo na težavnost poteka covid-19 pri slovenskih bolnikih, ki so preboleli to bolezen. Najprej smo izolirali DNA iz vzorcev polne venske krvi 106 bolnikov, ki so preboleli covid-19. Vzorce smo razdelili v tri skupine glede na težavnost poteka bolezni – blag, srednje težek in težek potek in izvedli genotipizacijo. Za analizo prvih štirih polimorfizmov rs1405655, rs721917, rs117169628 in rs67579710 smo uporabili metodo genotipizacije z uporabo hidrolizirajočih sond, za zadnji polimorfizem rs71325088 pa metodo genotipizacije z uporabo talilne krivulje. Pri analizi rezultatov smo izračunali frekvence variantnih alelov v slovenski populaciji in jih primerjali s frekvencami v drugih evropskih in svetovnih populacijah. Za polimorfizme rs1405655, rs721917 in rs67579710 smo dobili nižjo vrednost od evropske in svetovne, pri polimorfizmih rs117169628 in rs71325088 pa smo dobili večjo vrednost kot pri poročani evropski in svetovni populaciji. Pri proučevanju, ali obstaja povezava med prisotnostjo polimorfizma in težavnostjo poteka covid-19 pri slovenskih bolnikih, smo povezavo potrdili pri polimorfizmu rs11769628, in sicer naj bi polimorfizem imel zaščitno vlogo pred hujšo obliko bolezni. Pri ostalih polimorfizmih pa nismo ugotovili signifikantne povezave s težavnostjo poteka. Ugotovitve, ki smo jih pridobili tekom raziskovanja so pomembne, saj predstavljajo osnovo za nadaljne študije, ki bi pripomogle k vpeljavi teh ugotovitev v klinično prakso, hkrati pa predstavljajo prvi tak opis polimorfizmov, povezanih s covid-19, na slovenski populaciji.

Language:Slovenian
Keywords:covid-19, potek bolezni, genetski polimorfizmi, frekvenca variantnih alelov
Work type:Master's thesis/paper
Organization:FFA - Faculty of Pharmacy
Year:2024
PID:20.500.12556/RUL-161006 This link opens in a new window
Publication date in RUL:06.09.2024
Views:180
Downloads:33
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Secondary language

Language:English
Title:The impact of selected polymorphisms in the genes SLC22A31, SFTPD, THBS3, NR1H2 and LZTFL1 on the severity of COVID-19 disease
Abstract:
Since the first onset in 2019, covid-19 has had a major impact on the global population. It led to accelerated research, as scientists wanted to tackle risk factors involved in the disease's severity. They found that genetic changes play a substantial role in the course of the disease. For example, the rs1405655 polymorphism in the NR1H2 has been identified in the literature as a risk factor for severe neurological symptoms and, thus consequently, a more severe course of the disease. The polymorphism rs721917 in the SFTPD is associated with the penetration of the virus into the host cell by binding to the receptor for the angiotensin convertase 2. The polymorphism rs117169628 in the SLC22A31 has been associated with the co-regulation of transmembrane proteins and the consequent mediation of entry through the membrane. The rs67579710 polymorphism in the THBS3 has been related to the occurrence of thrombosis during the disease. A correlation between the polymorphism rs71325088 in the LZTFL1 and the entry of the virus through lung epithelial cells has been observed in the literature. The master’s thesis aimed to determine whether selected polymorphisms influence the severity of covid-19 in Slovenian patients who have overcome this disease. First, we isolated DNA from the whole venous blood of 106 patients who had recovered from covid-19. The samples were divided into three groups according to the severity of the disease - mild, moderate, and severe course, and genotyped. For the analysis of the first four polymorphisms (rs1405655, rs721917, rs117169628, and rs67579710), we used hydrolysis probes, while a high-resolution melting curve was used for detecting the polymorphism rs71325088. When analyzing the results, we calculated the frequencies of variant alleles in the Slovenian populations and compared them with the frequencies in other European and worldwide populations. We determined lower frequencies for polymorphisms rs1405655, rs721917, and rs67579710 compared to the European and worldwide populations. In contrast, for the polymorphisms rs117169628 and rs71325088, we determined a higher allele frequency than the European and worldwide populations. When analyzing the correlation between the occurrence of the polymorphism and the severity of the disease in the Slovenian population, we discovered that polymorphism rs11769628 may have a protective role. We did not find any significant associations between the other polymorphisms and the course of covid-19. The findings of this study are important, as they represent the basis for future studies that could help to translate these findings into clinical practice. At the same time, they represent the first description of covid-19-related polymorphisms in the Slovenian population.

Keywords:covid-19, course of the disease, genetic polymorphisms, frequency of variant alleles

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