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Polimorfizmi posameznih nukleotidov v genih ADARB1 in TPH2 in samomor v Sloveniji
ID Supej, Špela (Author), ID Videtič Paska, Alja (Mentor) More about this mentor... This link opens in a new window

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Abstract
V Sloveniji je med letoma 2010 in 2021 zaradi samomora umrlo v povprečju 407 oseb letno, kar nas po številu samomorov uvršča v sam svetovni vrh. Dejavnikov tveganja za samomorilno vedenje ne moremo pripisati zgolj enemu vzroku, saj gre večinoma za preplet hkratnega delovanja več dejavnikov, kot so npr. genetski dejavniki in dejavniki okolja, ki se izražajo v obliki psiholoških, bioloških in socioloških kazalcev. Pri samomorilnem vedenju je že bilo pokazano, da lahko pride do spremenjenega urejanja določenih genov na nivoju RNA. Ker sta v etiologijo samomorilnega vedenja vpletena tako serotoninski sistem kot tudi urejanje RNA, je ključno, da raziskujemo oba sistema hkrati. V okviru raziskave za magistrsko nalogo smo analizirali polimorfizme posameznih nukleotidov gena, ki je vključen v urejanje RNA, in sicer rs9983925 in rs4819035 v genu ADARB1, in pa tudi rs4290270 v genu TPH2, ki zapisuje za triptofan hidroksilazo 2 oz. hitrost določujoči encim sinteze serotonina v osrednjem živčevju. Cilj naše raziskave je bil ugotoviti, kateri izmed alelov izbranih polimorfizmov so različno zastopani v podskupinah oseb, ki so umrle zaradi samomora, v primerjavi s kontrolno skupino in na ta način prispevati k boljšemu poznavanju molekularne genetike samomorilnega vedenja. V raziskavo smo vključili večje število oseb slovenskega porekla, ki so umrle zaradi samomora, in kontrolno skupino – skupaj 690 oseb. Po izolaciji genomske DNA smo z uporabo hidrolizirajočih sond TaqMan in kvantitativnega PCR v realnem času določili, kateri aleli so prisotni v posameznem vzorcu, statistično analizo pa smo izvedli s pomočjo programa PLINK. Za polimorfizme TPH2 rs4290270, ADARB1 rs4819035 in ADARB1 rs9983925 nismo pri primerjavi podskupin umrlih zaradi samomora s kontrolno skupino ugotovili nobene statistično pomembne alelne oz. genotipske povezave s samomorom v slovenski populaciji.

Language:Slovenian
Keywords:ADARB1, TPH2, polimorfizem posameznih nukleotidov, samomor, urejanje RNA
Work type:Master's thesis/paper
Typology:2.09 - Master's Thesis
Organization:FKKT - Faculty of Chemistry and Chemical Technology
Year:2022
PID:20.500.12556/RUL-142974 This link opens in a new window
COBISS.SI-ID:135108611 This link opens in a new window
Publication date in RUL:07.12.2022
Views:558
Downloads:103
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Secondary language

Language:English
Title:Single nucleotide polymorphisms in ADARB1 and TPH2 genes and suicide in Slovenia
Abstract:
Between the years 2010 and 2021, the number of average yearly suicide deaths in Slovenia reached 407, making us one of the countries with the highest suicide rates in the world. The risk factors for suicidal behaviour cannot be attributed to a single cause, as they are usually a combination of multiple factors, such as genetic and environmental factors, which are expressed as psychological, biological and sociological indicators. It has already been shown that in the context of suicidal behaviour altered regulation of certain genes at the RNA level can occur. As both the serotonin system and RNA editing are involved in the aetiology of suicidal behaviour, it is crucial to investigate both systems simultaneously. In this research, we analysed single nucleotide polymorphisms rs9983925 and rs4819035 in the ADARB1 gene, that is involved in the RNA editing process, as well as rs4290270 in the TPH2 gene, which codes for tryptophan hydroxylase 2, the rate-determining enzyme of serotonin synthesis in the central nervous system. The aim of our study was to identify which of the alleles of the selected polymorphisms are differentially represented in the sub-groups of suicide victims compared to the control group and thus contribute to a better understanding of the molecular genetics of suicidal behaviour. Our study included a large number of suicide victims of Slovenian origin as well as a control group - 690 people in total. After isolation of genomic DNA, we used TaqMan hydrolysis probes and real-time quantitative PCR to determine which alleles were present in each sample. The statistical analysis was performed using PLINK program. For the TPH2 rs4290270, ADARB1 rs4819035 and ADARB1 rs9983925 polymorphisms, we did not find any statistically significant differences in genotype/allele frequency distribution between controls and Slovenian suicide victims.

Keywords:ADARB1, TPH2, single nucleotide polymorphism, suicide, RNA editing

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