Gender differences in N-glycosylation of plasma proteins in children with type 1 diabetes mellitus

Glikozilacija kao jedna od najčešćih i najsloženijih posttranslacijska modifikacija ima izniman utjecaj na konačnu funkciju modificiranog proteina, ali isto tako i sama je pod velikim utjecajem prisutnih fizioloških faktora. Šećerna bolest tipa 1 stanje je autoimunog narušavanja β - stanica Langerhansovih otočića ili samih molekula inzulina, čiji osnovni uzrok nije razjašnjen. U potrazi za objašnjenjem pozadine ove bolesti, odnosno u nastojanju pronalaska novih biomarkera koji bi na nju mogli ukazati, analiza glikozilacije ponudila se kao perspektivan pristup s obzirom na već ustanovljenu povezanost glikozilacije s različitim bolestima i patološkim stanjima, među kojima i s bolestima autoimune prirode. U istraživanju su sudjelovala 153 pacijenta u dobi između 2 i 19 godina, oboljela od šećerne bolesti tipa 1, kojima je pomoću HILIC-UPLC metode napravljen glikanski profil plazme. Dobiveni podaci obrađeni su i statistički uspoređeni prema spolu pomoću Mann-Whitney testa za nezavisne uzorke. U prvom dijelu istraživanja promatrane su pojedinačne glikanske skupine gdje je ustanovljena statistički značajna razlika za GP9, GP11, GP15 i GP17. Naknadno su ispitanici podijeljeni na dvije skupine, jednu mlađu od 10 godina i jednu stariju od 11 za ženske i 12 za muške ispitanike. Razlike među spolovima utvrđene su za GP6, GP9, GP11, GP17 i GP23 kod mlađe skupine, dok kod starije skupine nije ustanovljena statistički značajna razlika. U drugom dijelu istraživana usporedbom zastupljenosti pojedinih glikanskih osobina u profilima pacijenata nije ustanovljena statistički značajna razlika niti u jednoj kategoriji, kako kod mlađe tako ni kod starije skupine ispitanika. Dobivenim rezultatima potvrđena je prisutnost spolnih razlika u glikanskim profilima plazme pacijenata oboljelih od šećerne bolesti tipa 1, što ukazuje da razlike treba uzeti u obzir prilikom razvoja novih biomarkera i dijagnostičkih testova, odnosno eventualnih novih pristupa u terapiji.Glycosylation, as one of the most common and complex posttranslational modifications, has a profound effect on the final function of a modified protein but is also itself greatly affected by the physiological factors. Diabetes mellitus type 1 is a state where normal function of the beta cells of the pancreatic islets or the insulin molecules is compromised by an autoimmune response, even though the underlying cause is not yet known. In an effort to elucidate the cause of this disease and also to find new biomarkers that could possibly point to its development and presence, glycan analysis presented itself as a promising approach given the fact that glycosylation had already been connected to different diseases, some of which are also autoimmune. Plasma samples of 153 type 1 diabetes patients, aged between 2 and 19 years, were analyzed using a HILIC-UPLC method in a way that glycan profiles were created for every patient. Obtained data was then sorted and statistically analyzed by comparing glycosylation according to gender, using the Mann-Whitney test for independent samples. Individual glycan peaks were compared first, and analysis showed statistically significant difference between genders for GP9, GP11, GP15 and GP17. After sorting patients into two groups, one with patients younger than 10 years and another with patients older than 11 for females and 12 for males, differences were analyzed again. A younger group showed statistically significant difference in GP6, GP9, GP11, GP17 and GP23, but the older group didn't show any. Prevalences of several glycan characteristics in glycan profiles were also compared between genders, but statistically significant difference was not found for any of the analyzed characteristics in a younger group as well as in the older one. Results obtained in this study show that there is a gender difference between glycan profiles of type 1 diabetes patients. Those differences should be accounted for in development of new glycan-based diagnostic tests or therapeutics