Title (srp)

Sudskomedicinski i klinički značaj povezanosti polimorfizama gena FKBP5, NR3C1 i SKA2 i nivoa ekspresije odgovarajućih proteina sa poremećajem hipotalamo-hipofizno-adrenalne ose u etiologiji samoubistva: doktorska disertacija

Author

Radnić, Bojana, 1985-, 56595721

Contributor

Atanasijević, Tatjana, 1963-, 12617063
Petronijević, Nataša, 1963-, 12636007
Marić Bojović, Nađa, 1968-, 12764775
Popović, Vesna, 1964-, 12670055
Stojković, Oliver, 1969-, 9775975
Jovanović, Aleksandar, 1956-, 12456807
Nikolić, Tatjana, 1981-, 7075943

Description (srp)

Uvod. Značajan biološki faktor rizika za samoubistvo je poremećaj hipotalamo-hipofizno-adrenalne (HHA) ose. Proteini i odgovarajući geni koji se najćešće dovode u vezu sa disregulacijom negativne povratne sprege HHA ose su glukokortikoidni receptor (GR), FKBP5 i SKA2. Ciljevi. Analiza ekspresije navedenih proteina u prefrontalnom korteksu, amigdalama i hipokampusu i analiza učestalosti varijanti polimorfizama u genima NR3C1(rs41423247), FKBP5(rs1360780) i SKA2(rs7208505) kod žrtava suicida i osoba umrlih na drugi način. Predlog sudskomedicinskog vodiča za ekspertizu suicida kroz definisanje različitih, pa i bioloških, faktora rizika. Materijal i metode. Studije slučajeva i kontrola kroz koje se ispituju genetička i biohemijska etiologija suicida i deskriptivna studija koja analizira sudskomedicinski značajne rizikofaktore za izvršenje samoubistva. Podaci se odnose na umrle obdukovane na Institutu za sudsku medicinu. Posmatranu grupu čine slučajevi suicida, a kontrolnu osobe koje su umrle na drugi način. Ekspresija proteina u gorenavedenim delovima mozga analizirana je tehnikom Western blot. Odabrane varijacije genotipizovane su Real Time PCR metodom. Sociodemografski i psihijatrijski podaci o ispitanicima dobijeni su heteroanamnestičkim intervjuom. Rezultati. Visokoletalni načini suicida češći su sa alkoholemijom 1,5-3mg/mL i udruženi sa nižom ekspresijom FKBP5 proteina u hipokampusu. Prisustvo C alela u rs41423247 povećava rizik za suicid 3,48 puta. Ekspresija GR u amigdalama je niža u grupi suicida (p=0,016). Zaključci. U sagledavanju fenomena samoubistva, pored obdukcije, potrebni su: složen heteroanamnestički intervju, uzimanje uzoraka krvi za genetičko testiranje i uzoraka mozga za ispitivanje ekspresije proteina GR i FKBP5 i detaljna hemijsko-toksikološka analiza.

Description (srp)

Medicina - Molekularna medicina / Medicine- Molecular Medicine Datum odbrane: 16.09.2021.

Description (eng)

Introduction. An important biological risk factor for suicide is the hipothalamo-pituitary-adrenal (HPA) axis dysregulation. Proteins and corresponding genes that are most commonly associated with the HPA dysregulation are the glucocorticoid receptor (GR), FKBP5 i SKA2. Aims. The analysis of the abovementioned protein expression in the prefrontal cortex, amygdala and hippocampus and the analysis of the allel frequency in the following genes: NR3C1(rs41423247), FKBP5(rs1360780) i SKA2(rs7208505) in suicide victims and persons who died in a different manner. Proposition of a forensic guide for suicide expertise through defining different, including biological, risk factors. Material and methods. Case control studies investigating genetic and biochemical suicide etiology and a descriptive study analyzing forensic risk factors for suicide. All data refers to the autopsy cases from the Instute of Forensic Medicine. The cases consisted of completed suicides, while the control group was made of cases with a different manner of death. Protein expression was analyzed by Western blot technique. The chosen polymorphisms were genotypized by Real Time PCR method. Sociodemographic and psychiatric data was gained through a heteroanamnestic interview. Results. High lethality suicide methods are associated with blood alcohol levels 1,5-3mg/mL at the time of death as well as lower expression of FKBP5 in the hippocampus. The presence of C allel in rs41423247 represents a 3,48 times greater risk for suicide. The GR expression in the amygdala is lower in suicides (p=0,016). Conclusions. For a complete suicide perception, besides an autopsy, a complex heteroanamnestic interview, blood samples for genetic testing, brain samples for GR and FKBP5 protein expression investigation and a detailed toxicological analysis are needed.

Object languages

Serbian

Date

2021

Rights

Creative Commons License
This work is licensed under a
CC BY-NC-ND 2.0 AT - Creative Commons Attribution - Non-Commercial - No Derivative Works 2.0 Austria License.

CC BY-NC-ND 2.0 AT

http://creativecommons.org/licenses/by-nc-nd/2.0/at/

Subject

OSNO - Opšta sistematizacija nau?nih oblasti -- Medicina (29) -- Sudska medicina. Forenzi?ka medicina (2955)

Identifiers