doktorska disertacija
Tina Bizjak (Author), Igor But (Mentor), Uroš Potočnik (Co-mentor)

Abstract

Izhodišče: V preteklih raziskavah je že bila ugotovljena povezava med dednostjo in zdrsom medeničnih organov (ZMO), vendar pa do sedaj še nobena raziskava ni ciljano preučevala pomena dednosti pri izoliranem zdrsu maternice (ZM). V naši raziskavi kandidatnih genov smo skušali ugotoviti, ali genetske različice v šestih predhodno predlaganih lokusih kandidatov za ZMO, ki so bili pri ženskah evropskega porekla identificirani z asociacijsko študijo celotnega genoma, prav tako spremenijo tveganje pri naši skupini bolnic z ZM. Preiskovanke in metode dela: V raziskavo smo vključili 100 bolnic, ki so imele operacijo zaradi izoliranega popolnega ZM, in 105 zdravih žensk. Vse udeleženke so bile stare med 30 in 55 let. Po izolaciji genomske DNA iz periferne krvi smo genotipizirali šest polimorfizmov posameznega nukleotida (SNP), ki so bili predhodno povezani z ZMO. Opravili smo tudi analizo dejavnikov tveganja. Ekspresijo RNA smo določili na RNA in proteinih, ki smo jih izolirali iz sakrouterinih ligamentov pacientk in zdravih žensk s qPCR. Rezultati: Eden od šestih analiziranih SNP-jev je bil statistično povezan z ZM. Na lokusu kromosoma 20p13 smo ugotovili statistično pomembnost za model regresije faktorja tveganja za dominantni model alela T v SNP-ju rs6051098 (p = 0,046; OR: 1,93, CI: 1,01-3,66). Gen IDH3B je bil edini gen v lokusu 20p13, ki je bil v biopsijah sakrouterinega ligamenta pri ženskah z ZM statistično višje izražen v primerjavi s kontrolno skupino (p = 0,034). Analiza proteinov je pokazala trend k povišanemu izražanju proteina IDH3B pri bolnicah z ZM. Zaključek: Po našem najboljšem vedenju, smo kot prvi dokazali, da genetski dejavniki tveganja prispevajo k ZM in predlagali rs6051098 kot najboljši dejavnik tveganja, ki je povezan z ZM. Glede na pridobljene rezultate o ekspresiji predpostavljamo, da gen IDH3B igra vlogo pri patogenezi ZM.

Keywords

kandidatni geni;genetski polimorfizmi;genska ekspresija;zdrs medeničnih organov;zdrs maternice;Ginekologija;Disertacije;Maternica;Molekularna genetika;Polimorfizem;

Data

Language: Slovenian
Year of publishing:
Typology: 2.08 - Doctoral Dissertation
Organization: UM - University of Maribor
Publisher: T. Bizjak]
UDC: 618.14-056.7:577.214(043.3)
COBISS: 77700611 Link will open in a new window
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Other data

Secondary language: English
Secondary title: Genetic polymorphisms and gene expression associated with central uterine prolapse
Secondary abstract: Background: Evidence for a genetic association with pelvic organ prolapse (POP) was found in previous studies but no genetic studies differentiated different types of POP, such as uterine prolapse (UP). We conducted a candidate gene association study to investigate if genetic variants in six previously suggested candidate loci for POP identified in European pedigrees by genome-wide association study also modify the risk in our cohort of UP patients. Patients and methods: In our study, we included 100 patients between 30 and 55 years of age who had surgery due to total UP and 105 matched controls. After extracting the genomic DNA from peripheral blood, six single nucleotide polymorphisms (SNP) previously identified in genome-wide association study for POP were genotyped and the association analysis of contributing risk factors was calculated. RNA expression was determined on RNA isolated from sacrouterine ligaments of patients and controls using qPCR. Results: One out of six SNPs analyzed was associated with uterine prolapse in our cohort. A statistical significance for the dominant model for T allele for rs6051098 at chromosome 20p13 locus was found and remained significant with the risk factor regression model (p = 0.046; OR: 1.93, CI: 1.01-3.66). Gene IDH3B was the only gene in the 20p13 locus that was significantly upregulated in sacrouterine biopsies in women with UP compared to controls (p = 0.034). The protein analysis suggested a trend in the upregulation of the IDH3B protein in UP patients. Conclusions: To the best of our knowledge, we proved for the first time that genetic risk factors contribute to UP and suggested rs6051098 as best candidate risk factor associated with UP. According to expression data in sacrouterine tissue, we were the first to suggest IDH3B gene to play a role in UP pathogenesis.
Secondary keywords: candidate genes;genetic polymorphisms;gene expression;pelvic organ prolapse;uterine prolapse;Maternica;Ginekologija;Molekularna genetika;Genetski polimorfizem;Univerzitetna in visokošolska dela;
Type (COBISS): Dissertation
Thesis comment: Univ. v Mariboru, Medicinska fak.
Pages: X, 68 f.
ID: 12030193