Polimorfizmi u genima za čimbenike zgrušavanja i fibrinolize, glikoproteine trombocitne membrane i intermedijarne rizične čimbenike u djece s ishemijskim moždanim udarom

doctoral thesis

• Title (english): Polymorphisms of genes for coagulation and fibrinolysis factors, platelet membrane glycoproteins and intermediate risk factors in children with ischemic stroke
• Author: Andrea Čeri
• Mentor: Renata Zadro (mentor)
• Committee member: Karmela Barišić (predsjednik povjerenstva)
• Committee member: Vida Demarin (član povjerenstva)
• Committee member: Ivana Ćelap (član povjerenstva)
• Granter: University of Zagreb; Faculty of Pharmacy and Biochemistry; (Department of medical biochemistry and haematology); Zagreb
• Defense date and country: 2022-12-09, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Pharmacy; Pharmacy
• Universal decimal classification (UDC): 615 - Pharmacology. Therapeutics. Toxicology

Abstract

Ishemijski moždani udar (IMU) u djece je relativno rijedak poremećaj miješane etiologije koja je nerazjašnjena u približno 30 % slučajeva. Protrombotički poremećaji prepoznati su kao rizični čimbenik za nastanak IMU-a u
djece, ali su potencijalne pozadinske genske varijacije analizirane u oskudnom broju studija u specifičnim populacijama ili u odraslih, dok u djece rijetko ili uopće nisu analizirane. Kako se povezanost protrombotičkih
polimorfizama s IMU-om može razlikovati ovisno o geografskoj i etničkoj pripadnosti ispitivane populacije, a poznato je dodatno povećanje rizika u prisutnosti više od jednoga protrombotičkog rizičnog čimbenika, cilj ovoga istraživanja jest ispitati povezanost pojedinačnih polimorfizama u genima za čimbenike zgrušavanja, glikoproteinima trombocitne membrane i intermedijarne rizične čimbenike te potencijal zajedničke povezanosti s pojavom IMU-a u djece u Hrvatskoj ovisno o tipu, dobi nastanka i lokalizaciji IMU-a. Genotipizacija 21 polimorfizma u 13 gena kandidata provedena je iz uzorka DNA leukocita dobivenih nakon prikupljanja uzoraka ostatne periferne krvi od 185 djece starosne dobi do 18 godina s potvrđenom dijagnozom arterijskog IMU-a ili tromboze venskih sinusa mozga (CSVT) i 185 zdrave djece podudarne po dobi i spolu djeci s IMU-om. Dobiveni rezultati potvrdili su veću zastupljenost dječaka u svim podtipovima bolesti, osim perinatalnog
arterijskog IMU-a i CSVT-a te različite genetičke čimbenike za karakterizaciju različitih podtipova IMU-a u
djece. Na temelju dobivenih rezultata predložen je i algoritam ispitanih genetičkih čimbenika za IMU u djece za razlikovanje rizika nastanka podtipova bolesti te je uspostavljena baza podataka djece s IMU-om u Hrvatskoj. Rezultati predloženog istraživanja proširili su dosadašnja saznanja o potencijalnoj ulozi ispitanih genskih
varijacija u etiologiji IMU-a u djece u Hrvatskoj, ali i u općoj populaciji.

Abstract (english)

Ischemic paediattric stroke (IPS) is a relatively rare disorder of mixed aetiology that is unexplained in
approximately 30% of cases. Prothrombotic disorders are recognized as a risk factor for the development of IPS, but potential genetic variations in prothrombotic risk factors have been analysed in a limited number of studies in
specific populations or in adults, while in children they have been scarcely analysed or they have not been analysed at all. As the association of prothrombotic polymorphisms with IPS can differ depending on the geographic and ethnic categorisation of the population studied, and an additional increased risk is known in the presence of more than one prothrombotic risk factor, the aim of this study is to examine the association of individual polymorphisms in the genes coding clotting factors, platelet membrane glycoproteins and intermediate risk factors, and the potential of their joint association with the occurrence of IPS in children in Croatia depending on the type of IPS, age of onset and localization of the lesion. Genotyping of 21 polymorphisms in 13
candidate genes was performed in a DNA samples obtained from leukocytes after collecting residual peripheral blood samples from 185 children aged up to 18 years with confirmed diagnosis of arterial IPS (AIS) or cerebral venous sinus thrombosis (CSVT) and 185 healthy children matched by age and gender to children with IPS. Obtained results confirmed a higher frequency of AIS in boys and other subtypes, but not in perinatal AIS and CSVT. Also, it has been proven that different subtypes of IPS are caracterised by different genetic factors. Based
on the obtained results, an algorithm of tested genetic risk factors for IPS was proposed to distinguish the risk of subtypes of the disease, which established a database of children with IPS in Croatia. The results of the proposed
research expanded the previous knowledge about the potential role of the examined genetic variations in the aetiology of IPS in Croatia, with translational potential to the adult population.

• Keywords: djeca; ishemijski moždani udar; tromboza venskih sinusa mozga; trombofilija; genske varijacije; polimorfizmi; čimbenici zgrušavanja; čimbenici fibrinolize; glikoproteini trombocitne membrane; intermedijarni rizični čimbenici
• Keywords (english): children; paediatric ischemic stroke; cerebral sinovenous thrombosis; thrombophilia; genetic polymorphisms; coagulation factors; fibrinolysis factors; platelet membrane glycoproteins; intermediate risk factors
• Language: croatian
• URN:NBN: urn:nbn:hr:163:792961
• Promotion: 2022
• Study programme: Title: Pharmacy and biochemistry; Study programme type: university; Study level: postgraduate; Academic / professional title: doktor znanosti (doktor znanosti)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2022-12-16 16:30:46