Ispitivanje pojavnosti mutacija C677T i A1298C u genu za metilentetrahidrofolat-reduktazu u osoba oboljelih od psihičkih bolesti

master's thesis

• Title (english): Examination of methylenetetrahydrofolate-reductase mutations C677T and A1298C in persons with mental illnesses
• Author: Kristina Benjak
• Mentor: Karmela Barišić (mentor)
• Committee member: Karmela Barišić (predsjednik povjerenstva)
• Committee member: Željka Vanić (član povjerenstva)
• Committee member: Jasna Bingulac-Popović (član povjerenstva)
• Granter: University of Zagreb; Faculty of Pharmacy and Biochemistry; (Department of medical biochemistry and haematology); Zagreb
• Defense date and country: 2019-09-12, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Pharmacy; Pharmacy

Abstract

Psihički poremećaji su poremećaji funkcije neurotransmitora u mozgu koji dovode do nastanka kognitivnih, emocionalnih ili bihevioralnih disfunkcija. U svijetu preko 80 milijuna ljudi pati od psihičkih bolesti, a svake godine broj oboljelih se povećava. Do njihovog razvoja dolazi utjecajem genetičkih čimbenika, okolišnih čimbenika i kroničnog stresa. Kod oboljelih uzrokuju svakodnevnu subjektivnu patnju i smanjuju radnu sposobnost, kvalitetu života bolesnika, ali i njegove okoline.
Metilentetrahidrofolat reduktaza (MTHFR) je enzim koji ima značajnu ulogu u metabolizmu folata i metilaciji DNA, preko kojih utječe na sintezu neurotransmitora. Promijenjen metabolizam folata patofiziološka je podloga za nastanak psihičkih bolesti. Jedan od uzroka promijenjenog metabolizma folata je smanjena katalitička aktivnost MTHFR-a, kao posljedica genskog polimorfizma. Najznačajnije mutacije u genu za MTHFR povezane s razvojem psihičkih bolesti su C677T i A1298C. Ovo istraživanje je provedeno na 155 hospitaliziranih bolesnika Psihijatrijske bolnice „Sveti Ivan“ u Zagrebu i 101 zdravom dobrovoljnom darivatelju krvi sa svrhom ispitivanja povezanosti mutacija C677T i A1298C gena za MTHFR s razvojem psihičkih bolesti u hrvatskoj populaciji. Svim ispitanicima uzet je uz informirani pristanak uzorak periferne krvi s K2EDTA antikoagulansom. Provedena je izolacija DNA uz pomoć komercijalnog test kompleta QIAamp DNA Blood mini QIAcube kit (Qiagen GmbH, Hilden, Njemačka) na QIAcube uređaju i određivanje genotipova mutacija C677T i A1298C pomoću lančane reakcije polimeraze u stvarnom vremenu i alelne diskriminacije. Rezultati su podvrgnuti statističkoj usporedbi pomoću χ2-testa, omjera izgleda (OR) uz 95 % granice pouzdanosti (CI) i testom razlika proporcija.
Prema statističkoj usporedbi nije dokazana statistički značajna razlika u pojavnosti pojedinih genotipova i alela kod bolesnika s psihičkim bolestima i kontrolne skupine, za C677T mutaciju (OR 1,04; 95 % CI 0,628-1,727), za A1298C mutaciju (OR 1,002; 95 % CI 0,605-1,658). Rezultati ovog istraživanja nisu pokazali povezanost ispitivanih mutacija u genu za MTHFR s pojavnošću psihičkih bolesti na ispitivanom uzorku hrvatske populacije.

Abstract (english)

Psychiatric disorders are neurotransmitter function disorders in the brain that lead to cognitive, emotional or behavioral dysfunction. In the world, over 80 million people suffer from mental illness, and each year the number of patients is increasing. Their development is influenced by genetic factors, environmental factors and chronic stress. Psychiatric disorders cause everyday subjective suffering and reduce work ability, quality of life of a patient, but also his / her environment.
Methylentetrahydrofolate reductase (MTHFR) is an enzyme that plays a significant role in the metabolism of folate and methylation of DNA, which it affects the synthesis of neurotransmitters. Changed folate metabolism is a pathophysiological basis for the development of mental illness. One of the causes of the changed metabolism of folate is reduced activity of the MTHFR enzyme as a consequence of gene polymorphism. The most significant MTHFR mutations associated with the development of psychiatric diseases are C677T and A1298C. This study was conducted on 155 hospitalized patients of the Psychiatric Hospital "Sveti Ivan" in Zagreb and 101 healthy volunteer blood donors to examine the correlation of MTHFR C677T and A1298C mutations with the development of mental illnesses in Croatian population. All subjects was taken a peripheral blood sample with K₂EDTA anticoagulant with informed consent. DNA isolation with a commercial test kit QIAamp DNA Blood mini QIAcube kit (Qiagen GmbH, Hilden, Germany) on the QIAcube device was performed and MTHFR mutation genotypes were detected by real-time chain reaction polymerase and allelic discrimination. Results were subjected to statistical comparison by χ2-test, odds ratio (OR) with 95 % confidence interval (CI) and with proportial difference test.
There was no statistically significant difference in the occurrence of individual genotypes and alleles in patients with mental illness and control group, C677T mutation (OR 1.04, 95 % CI 0.628-1.727), A1298C mutation (OR 1.002, 95 % CI 0.605 -1.658). The results of this study did not demonstrate the correlation of both MTHFR mutations with the occurrence of mental illnesses on the examined sample of the Croatian population.

• Keywords: MTHFR-metilentetrahidrofolat-reduktaza; C677T mutacije; A1298C mutacije; psihičke bolesti
• Keywords (english): MTHFR-methylentetrahydrofolate-reductase; C677T mutations; A1298C mutations; psychiatric disorders
• Language: croatian
• URN:NBN: urn:nbn:hr:163:489894
• Study programme: Title: Pharmacy; Study programme type: university; Study level: integrated undergraduate and graduate; Academic / professional title: magistar/magistra farmacije (magistar/magistra farmacije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2021-04-23 11:00:35