Povezanost dva polimorfizma u genu za endotelnu sintazu dušikovoga oksida i hemoragijskoga moždanoga udara u djece

master's thesis

• Title (english): The association of two polymorphisms in the endothelial nitric oxide synthase gene and paediatric haemorrhagic stroke
• Author: Nikolina Damašek
• Mentor: Andrea Čeri (mentor)
• Mentor: Desiree Coen Herak (mentor)
• Committee member: Andrea Čeri (predsjednik povjerenstva)
• Committee member: Desiree Coen Herak (član povjerenstva)
• Committee member: Lidija Bach-Rojecky (član povjerenstva)
• Granter: University of Zagreb; Faculty of Pharmacy and Biochemistry; (Department of medical biochemistry and haematology); Zagreb
• Defense date and country: 2024-11-06, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Pharmacy; Medical Biochemistry

Abstract

Hemoragijski moždani udar (HMU) je akutni neurološki poremećaj koji nastaje uslijed rupture krvne žile, a stanje
je uzrokovano brojnim nasljednim i stečenim poremećajima. Endotelna sintaza dušikovog oksida ima ključnu
ulogu sintezi dušikovog oksida koji sudjeluje u cerebrovaskularnoj regulaciji, modulaciji razvoja neurona,
postnatalnom razvoju, ali je i medijator hipoksično-ishemijskoga oštećenja i oksidativnoga stresa. Polimorfizmi
NOS3 utječu na izražaj endotelne sintaze dušikovog oksida... More i dostupnost dušikovog oksida. Cilj ovoga istraživanja
bio je ispitati povezanost pojedinačnih polimorfizama NOS3 -786 T>C i 894 G>T i potencijalnoga haplotipa s
pojavom HMU-a u djece u Hrvatskoj. U istraživanje je bilo uključeno 32 djece s dijagnozom HMU-a starosne
dobi do 18 godina i 32 zdrave djece podudarne po dobi i spolu. U sve djece su genotipizirani polimorfizmi NOS3
-786 T>C i 894 G>T molekularno-genetičkom metodom, korištenjem kompleta za analizu CVD StripAssay® A
(ViennaLab Diagnostics GmbH, Beč, Austrija). U ispitivanju su se koristili uzorci genomske deoksiribonukleinske
kiseline svih ispitanika prethodno izdvojeni iz preostalih uzorka periferne krvi koji su korišteni za rutinske
laboratorijske analize. Rezultati statističke obrade podataka pokazali su podjednaku distribuciju genotipova i alela
za pojedinačne polimorfizme NOS3 -786 T>C i 894 G>T u djece s HMU-om i u kontrolnoj skupini, zbog čega
nije utvrđena statistički značajna povezanost ispitivanih polimorfizama s pojavom HMU-a u djece. Analiza
haplotipova NOS3 nije provedena budući da dobivena vrijednost parametra D' = 0,454 nije zadovoljila kriterije za
uključivanje dva polimorfizma u daljnju analizu. Daljnjim ispitivanjem na većem broju ispitanika i uključivanjem
analize više polimorfizama ili cijelih gena, primjerice, primjenom metoda sekvenciranja sljedeće generacije, moći
će se detaljnije istražiti povezanost endotelne sintaze dušikovoga oksida s pojavom HMU-a u djece. Less

Abstract (english)

Haemorrhagic stroke (HS) is an acute neurological disorder that occurs due to the rupture of a blood vessel. It is a
condition, caused by numerous hereditary and acquired disorders. Endothelial nitric oxide synthase plays a key role in
the synthesis of nitric oxide, which is involved in cerebrovascular regulation, modulation of neuronal development,
postnatal development, and also acts as a mediator of hypoxic-ischemic injury and oxidative stress. NOS3
polymorphisms affect the expression... More of endothelial nitric oxide synthase and the availability of nitric oxide. The aim of
this study was to examine the association between the NOS3 -786 T>C and 894 G>T polymorphisms, including its
haplotype, and the occurrence of haemorrhagic stroke in children in Croatia. The study included 32 children diagnosed
with HS up to the age of 18 years and 32 healthy children matched by age and sex that represented the control group. In
all children included in the study, NOS3 -786 T>C and 894 G>T polymorphisms were genotyped using a moleculargenetic method, the CVD StripAssay® A analysis kit (ViennaLab Diagnostics GmbH, Vienna, Austria). In this study,
samples of genomic deoxyribonucleic acid from all participants were used that were previously extracted from residual
peripheral blood samples used for routine laboratory analyses. The results of the statistical analysis showed an equal
distribution of genotypes and alleles for the individual NOS3 -786 T>C and 894 G>T polymorphisms in children with
HS and in the control group. Therefore, no statistically significant association was found between the examined
polymorphisms and the occurrence of HS in children. Analysis of NOS3 haplotypes was not performed since the obtained
value of the parameter D' = 0.454 have not meet the criteria for including two polymorphisms in further analysis. Further
studies with a larger number of participants and the inclusion of analyses of more polymorphisms or entire genes, for
example, using next-generation sequencing methods, could offer detailed investigation of the association between
endothelial nitric oxide synthase and the occurrence of haemorrhagic stroke in children. Less

• Keywords: hemoragijski moždani udar; endotelna NO sintaza; NOS3 polimorfizmi; djeca
• Keywords (english): haemorrhagic stroke; endothelial NO synthase; NOS3 polymorphisms; children
• Language: croatian
• URN:NBN: urn:nbn:hr:163:047804
• Study programme: Title: Medical biochemistry - integrated undergraduate and graduate - university study; Study programme type: university; Study level: integrated undergraduate and graduate; Academic / professional title: sveučilišni magistar medicinske biokemije i laboratorijske medicine (sveučilišni magistar medicinske biokemije i laboratorijske medicine)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2025-01-29 12:10:41