Povezanost varijanti gena za katehol-o-metil transferazu s poremećajem kognitivnih funkcija u shizofreniji

master's thesis

• Title (english): The association of catechol-o-methyil transferase genetic variants with cognitive impairment in schizophrenia
• Author: Ana Tkalčec
• Mentor: Nela Pivac (mentor)
• Mentor: Kristian Vlahoviček (mentor)
• Committee member: Aleksandar Vojta (predsjednik povjerenstva)
• Committee member: Domagoj Đikić (član povjerenstva)
• Committee member: Damjan Franjević (član povjerenstva)
• Committee member: Dunja Leljak-Levanić (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Biology); Zagreb
• Defense date and country: 2015-11-30, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Biology

Abstract

Shizofrenija je psihijatrijski poremećaj koji ozbiljno narušava život pojedinaca i njihovih najbližih. Narušene kognitivne sposobnosti kod pacijenata sa shizofrenijom najvjerojatnije su posljedica narušenog funkcioniranja dopaminergičkog sustava u prefrontalnom korteksu. Katehol-O-metil transferaza (COMT) je enzim koji regulira sinaptičku razinu dopamina i na taj način modulira centralnu dopaminergičku funkciju. Postoje naznake da bi funkcionalni polimorfizam rs4680 (Val108/158Met) gena COMT mogao utjecati na vezu izmeĎu kognicije i dopaminergičke aktivnosti u prefrontalnoj kori. Zbog nedostatka pouzdanih podataka i zbog velikog broja konfliktnih rezultata prisutnih u literaturi, cilj ovog diplomskog rada bio je istražiti postoji li povezanost polimorfizma rs4680 gena COMT i kognitivnih sposobnosti kod 501 bolesnika sa shizofrenijom. Po prvi put je istražena povezanost druga dva polimorfizma gena COMT (rs4818, rs4633) s kognitivnim simptomima u bolesnika sa shizofrenijom, s pretpostavkom da bi se navedeni polimorfizmi mogli nalaziti u neravnoteži udruživanja s polimorfizmom rs4680. Razumijevanje uloge genetičkih varijanti enzima COMT, kao važne karike dopaminergičkog sustava, moglo bi pomoći u shvaćanju doprinosa dopaminergičkog sustava razvoju kognitivnih poteškoća u shizofreniji.

Abstract (english)

Schizophrenia is a psychiatric disorder that severely affects patient’s life and life of his/her family. Impaired cognitive functions in patients with schizophrenia are most likely a consequence of the impaired function of the dopaminergic system in the prefrontal cortex. Catechol-O-metil transferase (COMT) is an enzyme that regulates the synaptic level of dopamine and in that way modulates the central dopaminergic function. There are indications that functional polymorphism rs4680 (Val108/158Met) of the COMT gene might affect the connection between cognition and dopaminergic activity in the prefrontal cortex. Due to the lack of reliable data and the large number of conflicting results in literature, the aim of this thesis was to explore the association between the polymorphism rs4680 of the COMT gene and the cognitive capabilities of 501 patients with schizophrenia. For the first time, the association of the other two polymorphisms of the COMT gene (rs4818, rs4633) with cognitive symptoms in patients with schizophrenia was explored, with the assumption that the aforementioned polymorphisms may exist in the linkage disequilibrium with the rs4680 polymorphism. Understanding the role of the COMT enzyme’s genetic variants, as an important part of the dopaminergic system, could help in understanding the contribution of the dopaminergic system in the development of cognitive deficit in schizophrenia.

• Keywords: dopamin; COMT; kognitivna funkcija; polimorfizam; shizofrenija
• Keywords (english): dopamine; COMT; cognitive function; polymorphism; schizophrenia
• Language: croatian
• URN:NBN: urn:nbn:hr:217:942368
• Study programme: Title: Molecular Biology; Study programme type: university; Study level: graduate; Academic / professional title: magistar/magistra molekularne biologije (magistar/magistra molekularne biologije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2017-04-24 08:54:52