Polimorfizam gena SULT2A1 i koncentracija dehidroepiandrosteron sulfata (DHEAS) u plazmi osoba s neurokognitivnim poremećajem

master's thesis

• Title (english): Polymorphism of SULT2A1 gene and plasma levels of dehydroepiandrosterone sulfate (DHEAS) in individuals with neurocognitive disorder
• Author: Nikola Balić
• Mentor: Dubravka Švob Štrac (mentor)
• Mentor: Dubravka Hranilović (komentor)
• Committee member: Dubravka Hranilović (predsjednik povjerenstva)
• Committee member: Martina Šeruga Musić (član povjerenstva)
• Committee member: Julija Erhardt (član povjerenstva)
• Committee member: Silvija Černi (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Biology); Zagreb
• Defense date and country: 2023-09-21, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Biology

Abstract

Neurosteroid dehidroepiandrosteron sulfat (DHEAS) uključen je u brojne moždane funkcije,
uključujući učenje, pamćenje, ponašanje, neurogenezu, neuralnu plastičnost i neuroprotekciju.
Istraživanja su utvrdila povezanost između endogenih koncentracija DHEAS-a i demencije, te
kognitivnih sposobnosti osoba tijekom starenja. Međutim, u osoba s demencijom utvrđene su
snižene, ali i povišene koncentracije DHEAS-a povezane s kognitivnim disfunkcijama, dok je
pozitivan učinak DHEAS-a na kognitivne funkcije primijećen samo u nekim studijama. Cilj rada
bio je istražiti razlike u plazmatskoj koncentraciji DHEAS-a te raspodjeli genotipova polimorfizma
rs2637125 gena SULT2A1, koji kodira za enzim sulfotransferazu 2A1, odgovornu za pretvorbu
dehidroepiandrosterona u sulfatni oblik, u 213 osoba s blagim i 91 osobe s velikim
neurokognitivnim poremećajem. Također sam istražio utječu li varijacije u genu SULT2A1 na
koncentraciju DHEAS-a u plazmi te postoji li njihova povezanost s težinom neurokognitivnog
poremećaja. Dijagnoza demencije postavljena je prema DSM-5 kriterijima, a kognitivni simptomi
evaluirani su testovima procjene mentalnog stanja. Iz krvi osoba izolirao sam plazmu i DNA. U
plazmi sam odredio koncentraciju DHEAS-a metodom ELISA, dok sam genotipizaciju proveo
metodom lančane reakcije polimerazom u stvarnom vremenu. Istraživanje nije utvrdilo značajne
razlike u plazmatskoj koncentraciji DHEAS-a između osoba s blagim i velikim neurokognitivnim
poremećajem, kao niti značajnu povezanost SULT2A1 polimorfizma s težinom neurokognitivnog
poremećaja.

Abstract (english)

Neurosteroid dehydroepiandrosterone sulfate (DHEAS) is involved in numerous brain functions,
including learning, memory, behavior, neurogenesis, neural plasticity, and neuroprotection.
Research suggested association of endogenous DHEAS concentrations with dementia and cognitive
functions during aging. However, in dementia patients, both decreased and increased DHEAS
concentrations were associated with cognitive dysfunctions, while DHEAS beneficial effects on
cognition were observed only in some studies. The study aim was to investigate differences in
DHEAS plasma concentration and genotype distribution of rs2637125 polymorphism in SULT2A1
gene, coding for enzyme sulfotransferase 2A1, responsible for conversion of
dehydroepiandrosterone into its sulfate form, in 213 people with mild and 91 people with severe
neurocognitive disorder. I also investigated whether variations in SULT2A1 gene affect plasma
DHEAS concentration and their association with neurocognitive disorder severity. Dementia was
diagnosed according to DSM-5 criteria, and cognitive symptoms were evaluated using mental state
examination tests. Plasma and DNA were isolated from blood of subjects. Plasma DHEAS
concentration was determined using ELISA method, while genotyping was performed using real
time polymerase chain reaction.The study did not find any significant differences in DHEAS plasma
concentration between individuals with mild and severe neurocognitive disorder, or any significant
association of SULT2A1 polymorphism with severity of neurocognitive disorder.

• Keywords: neurosteroid; demencija; kognicija; sulfotransferaza 2A1; SNP; genotipovi
• Keywords (english): neurosteroid; dementia; cognition; sulfotransferase 2A1; SNP; genotypes
• Language: croatian
• URN:NBN: urn:nbn:hr:217:651986
• Project: Number: IP-2019-04-6100; Title: Terapijski potencijal neurosteroida i neurotrofina u demenciji; Title: Therapeutic potential of neurosteroids and neurotrophins in dementia; Acronym: TePoNeDe; Leader: Dubravka Švob Štrac; Jurisdiction: Croatia; Funder: HRZZ; Funding stream: IP
• Study programme: Title: Experimental Biology; Study programme type: university; Study level: graduate; Academic / professional title: magistar/magistra eksperimentalne biologije (magistar/magistra eksperimentalne biologije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access; Embargo expiration date: 2024-09-21
• Created on: 2023-10-16 10:23:18