Show simple item record

Functional analysis of FIIc.1787G>A (protrombin, Belgrade) and FIIc.*64_*66del gene variants and their assotiation with trombophilia

dc.contributor.advisorĐorđević, Valentina
dc.contributor.otherRadojković, Dragica
dc.contributor.otherĐorđević, Valentina
dc.contributor.otherRadojković, Dragica
dc.contributor.otherSavić-Pavićević, Dušanka
dc.creatorGvozdenov, Maja Ž.
dc.date.accessioned2017-07-10T15:03:06Z
dc.date.available2017-07-10T15:03:06Z
dc.date.available2020-07-03T08:08:21Z
dc.date.issued2017-05-05
dc.identifier.urihttp://eteze.bg.ac.rs/application/showtheses?thesesId=5098
dc.identifier.urihttp://nardus.mpn.gov.rs/handle/123456789/8364
dc.identifier.urihttps://fedorabg.bg.ac.rs/fedora/get/o:15910/bdef:Content/download
dc.identifier.urihttp://vbs.rs/scripts/cobiss?command=DISPLAY&base=70036&RID=1025154994
dc.description.abstractProtrombin predstavlja zimogen trombina (koagulacinog faktora II), koji ima centralnu ulogu u održanju hemostazne ravnoteže. Zahvaljujući alosteričnoj regulaciji, trombin može da vrši i prokoagulantnu i antikoagulantnu funkciju. Region 3' kraja gena za protrombin ima nekanonsku organizaciju i podložan je nastanku genskih varijanti koje mogu imati značajnu ulogu u regulaciji ekspresije i funkcije protrombina. Do sada opisane varijante u ovom regionu su povezivane sa povišenom ekspresijom protrombina koja može dovesti do hiperkoagulacije i povećane sklonosti ka trombozama, odnosno trombofiliji. U Laboratoriji za molekularnu biologiju, Instituta za molekularnu genetiku i genetičko inženjerstvo, u 3' kraju gena za protrombin opisane su FIIc.1787G>A i FIIc.*64_*66del varijante čiji mehanizmi do sada nisu rasvetljeni. Varijanta FIIc.1787G>A (protrombin Beograd) se nalazi u poslednjem egzonu gena za protrombin i dovodi do aminokiselinske zamene Arg596Gln u proteinu. Ova varijanta se nalazi u regionu za koji se vezuju joni natrijuma, neophodni za prokoagulantnu aktivnost trombina, kao i prirodni trombinski inhibitor- antitrombin. Varijanta FIIc.*64_*66del se nalazi u 3' netranslatirajućem regionu gena i predstavlja deleciju 3 nukleotida. Imajući u vidu pozicije u različitim strukturnim elementima 3' kraja gena, pretpostavlja se da su mehanizmi delovanja ovih varijanti različiti. Prvi deo studije je imao za cilj određivanje učestalosti FIIc.1787G>A i FIIc.*64_*66del varijanti kod 353 pacijenta sa različitim trombotičkim poremećajima i 250 zdravih ispitanika u srpskoj populaciji. Pacijenti su u zavisnosti od tipa trombotičkog poremećaja podeljeni u 4 grupe: tromboze dubokih vena (94 pacijenta), izolovani plućni embolizam (104 pacijenta), kombinovani trombotički poremećaji (49 pacijenata) i spontani pobačaji (106 pacijentkinja). Drugi deo studije je obuhvatio ex vivo analize, s ciljem da se ispita uticaj navedenih varijanti na funkcionalnost i raspoloživu količinu protrombina u plazmi ispitanika...sr
dc.description.abstractProthrombin is a zymogen of thrombin (coagulation factor II), which plays a central role in maintaining hemostatic balance. Due to the allosteric regulation, thrombin has dual function: procoagulant and anticoagulant. The 3' end of prothrombin gene has noncanonical organization, which is susceptible to the genetic variants that might have a significant role in the regulation of prothrombin expression and function. Variants reported within this region lead to increased prothrombin expression which is associated with hypercoagulability and increased tendency to thrombophilia. In the Laboratory for Molecular Biology at the Institute of Molecular Genetics and Genetic Engineering, we have reported FIIc.1787G>A and FIIc.*64_*66del variants in 3' end of prothrombin gene, but their mechanisms of action have not been elucidated so far. The FIIc.1787G>A (prothrombin Belgrade) is located in the last exon of the prothrombin gene, leading to amino acid substitution Arg596Gln in the protein. This variant is positioned in a region of antithrombin (thrombin inhibitor) binding site, as well as in Na+ binding loop, which is significant for procoagulant activity of thrombin. The FIIc.*64_*66del is located in the 3' untranslated gene region and represents a deletion of three nucleotides. Taking into account the position of these two variants in different structural elements of 3' end of prothrombin gene, it is assumed that they differ in the mechanisms of action. In the first part of the study, we determined the frequency of FIIc.1787G>A and FIIc.*64_*66del variants in 353 patients with thrombotic disorders and 250 healthy subjects in Serbian population. Patients were divided into 4 groups according to the type of thrombotic disorders: deep vein thrombosis (94 patients), isolated pulmonary embolism (104 patients), combined thrombotic disorders (49 patients) and fetal loss (106 patients). The second part of the study included the ex vivo analyses, with aim to investigate the impact of these variants on the functionality and available amount of prothrombin in the subjects plasma samples...en
dc.formatapplication/pdf
dc.languagesr
dc.publisherУниверзитет у Београду, Биолошки факултетsr
dc.relationinfo:eu-repo/grantAgreement/MESTD/Basic Research (BR or ON)/173008/RS//
dc.rightsopenAccessen
dc.sourceУниверзитет у Београдуsr
dc.subjectFIIc.1787G>Asr
dc.subjectFIIc.1787G>Aen
dc.subjectprothrombin Belgradeen
dc.subjectFIIc.*64_*66delen
dc.subjectprothrombinen
dc.subject3end of geneen
dc.subjectantithrombin resistanceen
dc.subjectgene expression regulationen
dc.subjectthrombophiliaen
dc.subjectprotrombin Beogradsr
dc.subjectFIIc.*64_*66delsr
dc.subjectprotrombinsr
dc.subject3' kraj genasr
dc.subjectantitrombin rezistencijasr
dc.subjectregulacija genske ekspresijesr
dc.subjectthrombofilijasr
dc.titleFunkcionalna analiza genskih varijanti FIIc.1787G>A (protrombin, Beograd) i FIIc.*64_*66del i njihova povezanost sa trombofolijomsr
dc.title.alternativeFunctional analysis of FIIc.1787G>A (protrombin, Belgrade) and FIIc.*64_*66del gene variants and their assotiation with trombophiliaen
dc.typedoctoralThesis
dc.rights.licenseBY-NC-ND
dcterms.abstractЂорђевић, Валентина; Радојковић, Драгица; Ђорђевић, Валентина; Радојковић, Драгица; Савић-Павићевић, Душанка; Гвозденов, Маја Ж.; Функционална анализа генских варијанти ФИИц.1787Г>A (протромбин, Београд) и ФИИц.*64_*66дел и њихова повезаност са тромбофолијом; Функционална анализа генских варијанти ФИИц.1787Г>A (протромбин, Београд) и ФИИц.*64_*66дел и њихова повезаност са тромбофолијом;
dc.identifier.fulltexthttp://nardus.mpn.gov.rs/bitstream/id/1870/IzvestajKomisije11048.pdf
dc.identifier.fulltexthttp://nardus.mpn.gov.rs/bitstream/id/1869/Disertacija.pdf


Files in this item

Thumbnail
Thumbnail

This item appears in the following Collection(s)

Show simple item record