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Roles of polymorphisms and expression of genes coding for chemokines CX3C ligand 1 and CXC ligand 16 and their receptors in the development and progression of multiple sclerosis in Serbia

dc.contributor.advisorŽivković, Maja
dc.contributor.otherSavić-Pavićević, Dušanka
dc.contributor.otherDinčić, Evica
dc.creatorStojković, Ljiljana S.
dc.date.accessioned2016-01-05T11:48:24Z
dc.date.available2016-01-05T11:48:24Z
dc.date.available2020-07-03T08:11:32Z
dc.date.issued2013-09-20
dc.identifier.urihttp://nardus.mpn.gov.rs/handle/123456789/2155
dc.identifier.urihttp://eteze.bg.ac.rs/application/showtheses?thesesId=1108
dc.identifier.urihttps://fedorabg.bg.ac.rs/fedora/get/o:7848/bdef:Content/download
dc.identifier.urihttp://vbs.rs/scripts/cobiss?command=DISPLAY&base=70036&RID=1024587442
dc.description.abstractMultipla skleroza je hroniĉna inflamatorna, autoimunska, demijelinizaciona i neurodegenerativna bolest centralnog nervnog sistema (CNS-a). Hemokini i njihovi receptori predstavljaju znaĉajne medijatore inflamacije koji uĉestvuju u patogenezi odreĊenih hroniĉnih inflamatornih i autoimunskih bolesti meĊu kojima je i multipla skleroza. Ciljni hemokini u ovoj studiji, CX3C ligand 1 (CX3CL1) i CXC ligand 16 (CXCL16), specifiĉni su po tome što postoje u dve forme - kao transmembranski adhezivni molekuli i kao solubilni hemoatraktanti koji nastaju nakon proteolitiĉkog seĉenja vanćelijskih hemokinskih domena njihovih transmembranskih formi. U toku inflamatornog odgovora, na membrani endotelnih vaskularnih ćelija eksprimirani su CX3CL1 i CXCL16, a na membrani leukocita receptori za CX3CL1 (CX3CR1) i CXCL16 (CXCR6), te ovi hemokini i njihovi receptori posreduju u prodiranju leukocita iz krvi u tkivo zahvaćeno inflamacijom, podsticanjem hemotaksije i adhezije leukocita za aktivirani endotel krvnog suda. Ova studija obuhvata genetsko-epidemiološku analizu polimorfizama zamena pojedinaĉnih nukleotida u kodirajućim regionima gena, koje rezultuju zamenama aminokiselina. To su polimorfizmi V249I i T280M u genu za CX3CR1, i I123T i A181V u genu za CXCL16. U prethodnim studijama je pokazano da ovi genski polimorfizmi menjaju funkcionalna svojstva CX3CR1 i CXCL16, kao i da su asocirani sa patogenezom odreĊenih hroniĉnih inflamatornih bolesti. Uzimajući to u obzir, ova studija je imala za cilj da po prvi put ispita asocijaciju navedenih polimorfizama u genima za CX3CR1 i CXCL16 sa nastankom i progresijom multiple skleroze. Primenom alel-specifiĉne PCR metode i PIRA PCR-RFLP metode detektovani su genotipovi polimorfizama V249I i T280M u genu za CX3CR1, kod zdravih kontrola i pacijenata sa multiplom sklerozom. UtvrĊeno je da haplotip I249T280 u genu za CX3CR1 ima znaĉajno veću uĉestalost kod pacijenata sa relapsno-remitentnom (RR) formom, u odnosu na pacijente sa sekundarno-progresivnom (SP) formom multiple skleroze, što znaĉi da ovaj haplotip ima protektivni efekat na progresiju RR u SP formu bolesti...sr
dc.description.abstractMultiple sclerosis is a chronic inflammatory, autoimmune, demyelinating and neurodegenerative disease of the central nervous system (CNS). Chemokines and their receptors are important mediators of inflammation, which are involved in pathogenesis of certain chronic inflammatory and autoimmune diseases including multiple sclerosis. Chemokines of interest in this study, CX3C ligand 1 (CX3CL1) and CXC ligand 16 (CXCL16), are specific in that they can exist either as transmembrane adhesion molecules or soluble chemoattractants being generated by proteolytic cleavage of their transmembrane forms’ extracellular domains. During the inflammatory response, CX3CL1 and CXCL16 are expressed on the surface of vascular endothelium, while the leukocytes produce membrane receptors for CX3CL1 (CX3CR1) and CXCL16 (CXCR6). Therefore, these chemokines and their receptors mediate the infiltration of leukocytes from blood into the inflamed tissue areas, by stimulation of both chemotaxis and adhesion of leukocytes to the activated endothelium of blood vessels. This study is based on genetic epidemiological analysis of single nucleotide polymorphisms, which are located in the coding regions of genes and result in amino acids’ substitutions. These are V249I and T280M substitutions in the gene coding for CX3CR1, and I123T and A181V substitutions in the gene coding for CXCL16. In previous studies these polymorphisms have been associated with the functional properties of CX3CR1 and CXCL16 as well as the pathogenesis of certain chronic inflammatory diseases. Therefore, this study aimed to investigate the association of the polymorphisms in CX3CR1 and CXCL16 genes with the development and progression of multiple sclerosis. Using the allele-specific PCR and PIRA PCR-RFLP methods, genotypes of CX3CR1 V249I and T280M polymorphisms were detected in healthy controls and patients with multiple sclerosis. Following statistical analysis showed significantly higher frequency of CX3CR1 I249T280 haplotype in patients with relapsingremitting (RR) form, compared to patients with secondary-progressive (SP) form of multiple sclerosis, so this haplotype had a protective effect on progression of RR to SP form of the disease...en
dc.formatapplication/pdf
dc.languagesr
dc.publisherУниверзитет у Београду, Биолошки факултетsr
dc.relationinfo:eu-repo/grantAgreement/MESTD/Integrated and Interdisciplinary Research (IIR or III)/41028/RS//
dc.relationinfo:eu-repo/grantAgreement/MESTD/Basic Research (BR or ON)/175085/RS//
dc.rightsopenAccessen
dc.sourceУниверзитет у Београдуsr
dc.subjectmultipla sklerozasr
dc.subjectmultiple sclerosisen
dc.subjectgensr
dc.subjectpolimorfizamsr
dc.subjectekspresijasr
dc.subjecthemokinsr
dc.subjectCX3CL1sr
dc.subjectCXCL16sr
dc.subjectCX3CR1sr
dc.subjectCXCR6sr
dc.subjectgeneen
dc.subjectpolymorphismen
dc.subjectexpressionen
dc.subjectchemokineen
dc.subjectCX3CL1en
dc.subjectCXCL16en
dc.subjectCX3CR1en
dc.subjectCXCR6en
dc.titleUloga polimorfizama i ekspresije gena za hemokine CX3C ligand 1 i CXC ligand 16 i njihove receptore u nastanku i progresiji multiple skleroze u Srbijisr
dc.titleRoles of polymorphisms and expression of genes coding for chemokines CX3C ligand 1 and CXC ligand 16 and their receptors in the development and progression of multiple sclerosis in Serbiaen
dc.typedoctoralThesis
dc.rights.licenseBY-NC-ND
dcterms.abstractЖивковић, Маја; Динчић, Евица; Савић-Павићевић, Душанка; Стојковић, Љиљана С.;
dc.identifier.fulltexthttp://nardus.mpn.gov.rs/bitstream/id/2533/Disertacija.pdf


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