Title Glikanski i genetski biomarkeri posttraumatskog strasnog poremećaja Title (english) Glycomic and genetic biomarkers of posttraumatic stress disorder Author Lucija Tudor Mentor Nela Pivac (mentor)Committee member Lipa Čičin-Šain (predsjednik povjerenstva)Committee member Marijana Braš (član povjerenstva)Committee member Miranda Mladinić Pejatović (član povjerenstva)Granter University of Rijeka Defense date and country 2020, Croatia Scientific / art field, BIOTECHNICAL SCIENCES Universal decimal classificationUDC ) 577 - Biochemistry. Molecular biology. Biophysics Abstract Posttraumatski stresni poremećaj (PTSP) je psihijatrijski poremećaj s kompleksnom etiologijom i bez validiranih biomarkera. Glikozilacija proteina je proces kovalentnog vezanja sećera na proteine te može značajno utjecati na njihovu biološku funkciju. Iako ovaj proces nema predefinirani kalup, postoji velik broj gena koji kodiraju za enzime i proteine uključene
u metabolizam i vezanje glikana. Cilj ovog istraživanja bio je analizirati glikozilacijski profil proteina u plazmi i imunoglobulina
G (IgG) kod ispitanika sa i bez PTSP-a te ispitati povezanost 12 polimorfizama s PTSP-om i zastupljenosti pojedinih N-glikana. N-glikom određen je pomoću visokoprotočne tekućinske kromatografije, a genotipizacija je provedena metodom lančane reakcije polimeraze u stvarnom vremenu. Razlike u N-glikomu između ispitanika sa i bez PTSP-a te između nositelja pojedinih genotipova i haplotipova odabranih polimorfizama, analizirani su u dvije neovisne kohorte. Ispitanici s PTSP-om imali su značajno promijenjen N-glikom plazme, ali ne i IgG-a, pri čemu su 4 N-glikana bila značajno povišena, a 2 značajno snižena u odnosu na kontrolne ispitanike. GG genotip s obzirom na HNF1A-AS1 rs7953249 bio je značajno rjeđe prisutan kod ispitanika
s PTSP-om, dok ostali testirani polimorfizmi nisu bili povezani s dijagnozom. 2 polimorfizma HNF1A su pokazali najveću povezanost s glikozilacijom u PTSP-u, odnosno sa sržno fukoziliranim IgG glikanima te visokorazgranatim N-glikanima u plazmi. 2 polimorfizma FUT8 bila su povezana sa sržno fukoziliranim N-glikanima, a B3GAT1 rs7928758 je bio značajno povezan s dva N-glikana u plazmi. Značajnost ostalih polimorfizama s glikozilacijom nije bila potvrđena u obje kohorte. Rezultati ove studije pokazali su sličnost N-glikoma u PTSP-u s onima primijećenima u upalnim procesima, autoimunim bolestima i drugim psihijatrijskim poremećajima te upućuju na potencijalnu regulatornu ulogu glikozilacije, upalnih čimbenika i HNF1A u razvoju i progresiji PTSP-a.
Abstract (english) Posttraumatic stress disorder (PTSD) is psychiatric disorder with complex etiology and no validated biomarkers. Protein glycosylation is a modification involving covalent binding of sugars on proteins and can radically change their biological properties. Although the process of sugar binding is not predefined, there are numerous genes that encode for the enzymes involved in metabolism and assembly of glycans. The aim of this study was to analyze plasma and immunoglobulin G (IgG) glycosylation patterns in subjects with and without PTSD and to examine the association of 12
polymorphisms with PTSD and distribution of specific N-glycans. N-glycome was determined using high performance liquid chromatography while genotyping was performed using realtime PCR. Differences in N-glycome between subjects with and without PTSD between carriers of different genotypes and haplotypes of selected polymorphisms, were anayzed in two separate cohorts. Patients with PTSD had significantly changed plasma, but not IgG, N-glycome, where 4 Nglycans were significantly higher and 2 significantly lower compared to control subjects. GG genotype carriers of HNF1A-AS1 rs7953249 were significantly less present in subjects with PTSD, while other polymorphisms were not associated with diagnosis. 2 polymorphisms HNF1A showed the highest association with glycosylation in PTSD, specifically with corefucosylated IgG N-glycans and highly branched and sialyated plasma glycans. 2 polymorphisms FUT8 were associated with core-fucosylated N-glycans, while B3GAT1 rs7928758 was associated with 2 N-glycans in plasma. Significant association of other polymorphisms with glycosylation was not replicated in both cohorts. This study showed similar glycosylation patterns in PTSD with ones seen in inflammatory processes, autoimmune diseases and other psychiatric disorders and implicates potential regulatory role of glycosylation, inflammatory factors and HNF1A in development and progression of PTSD.
Keywords
PTSP
biomarkeri
N-glikozilacija
GWAS
upala
Keywords (english)
PTSD
biomarkers
N-glycosylation
GWAS
inflammation
Language croatian URN:NBN urn:nbn:hr:193:893254 Promotion 2021 Study programme Title: Medicinal chemistry Type of resource Text File origin Born digital Access conditions Closed access Terms of use Created on 2021-12-16 13:12:14
