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dc.contributor.advisorĐonović, Nela
dc.contributor.otherMilošević-Đorđević, Olivera
dc.contributor.otherSrećković, Sunčica
dc.contributor.otherŠarenac-Vulović, Tatjana
dc.contributor.otherStevanović, Jevrosima
dc.creatorSavić, Borivoje
dc.date.accessioned2020-10-24T12:35:13Z
dc.date.available2020-10-24T12:35:13Z
dc.date.issued2020-07-28
dc.identifier.urihttp://eteze.kg.ac.rs/application/showtheses?thesesId=7556
dc.identifier.urihttps://fedorakg.kg.ac.rs/fedora/get/o:1271/bdef:Content/download
dc.identifier.urihttps://nardus.mpn.gov.rs/handle/123456789/17550
dc.descriptionUvod. U gotovo 90% odrasle populacije prisutna su antitela prema tipu 1 Herpes simplex (HSV-1) virusa. Interferoni tipa III (IFN-λ) imaju veoma značajnu antivirusnu i antiinflamacijsku aktivnost, što je od posebnog značaja kod rekurentnog herpetičnog keratitisa. Epigenetska priroda reaktivacije HSV-1, između ostalog, može zavisiti od prisustva i koncentracija dokazanih epigentskih modulatora kao što su vitamin B12 i folna kiselina, koji su uključeni u proces metilacije molekula DNK. Ciljevi. Cilj studije je da se istraži moguća povezanost između IL28B genotipa domaćina i predispozicije za rekurentni stromalni herpetični keratitis. Takođe, cilj ovog istraživanja je i analiza moguće povezanosti između koncentracija vitamina B12 i folne kiseline u krvi sa razvojem rekuretnog herpetičnog keratitisa. Metode. Ispitivanje je sprovedeno na uzorku od osamdeset pacijenata starijih od 18 godina, oba pola, koji su u anamnezi imali pojavu rekurentnog herpesvirus hominis labialis (HSL). Svi ispitanici su testirani na prisustvo IgG antitela specifičnih za HSV-1, kako bi se kod seropozitivnih pojedinaca tipizirao gen IL28B (rs12979860snp). Sedamdeset i pet seropozitivnih ispitanika uključeno je u studiju. Dvadeset i četiri pacijenata imala su rekurentni herpetični keratitis sa posledičnim ožiljavanjem rožnjače i značajnim smanjenjem vidne oštrine. Ukupna DNK izolovana je iz uzoraka krvi ispitanika. Ispitanicima sa recidivirajućim herpetičnim keratitisom, dodatno je uzeto 2ml periferne venske krvi za određivanje nivoa folne kiseline i vitamina B12 u akutnoj fazi recidiva herpetične bolesti oka. Rezultati. U našem istraživanju pokazana je statistički značajna povezanost između pojave rekuretnog HSV keratitisa i dva jednonukleotidna polimorfizma (SNP) za genotip IL28B (CCrs12979860 i CTrs12979860, p<0.05). Takođe, prema rezultatima naše studije, svi pacijenti su imali niže vrednosti vitamina B12 i folne kiseline u serumu u akutnoj fazi recidivirajućeg herpetičnog keratitisa. Zaključak. Rezultati naše studije pokazuju da se klinička manifestacija rekurentne HSV-1 infekcije može povezati sa polimorfizmom IL28B gena. Reaktivacija virusa HSV-1 može biti povezana sa minimalnim nedostatkom vitamina B12 i folne kiseline tokom latentne faze bolesti, zbog epigenetske prirode HSV-1 virusa.sr
dc.descriptionIntroduction. Herpes simplex (HSV-1) type 1 antibodies are present in almost 90% of the adult population. Type III interferons (IFN-λ) have very significant antiviral and anti-inflammatory activity, which is of particular importance in recurrent herpetic keratitis. The epigenetic nature of HSV-1 reactivation may depend, among other things, on the presence and concentrations of proven epigenetic modulators such as vitamin B12 and folic acid involved in the DNA methylation process. Objectives. The aim of this study is to investigate the possible association between IL28B host genotype and the predisposition to recurrent stromal herpetic keratitis. Also, the aim of the study is to find out the possible relationship between vitamin B12 and folic acid concentrations in blood and recurrent herpetic keratitis. Methods. The study was conducted on a sample of eighty patients over 18 years of age, of both genders with a history of recurrent herpesvirus hominis labialis (HSL). All subjects were tested for the presence of HSV-1-specific IgG in order to typify IL28B genes (rs12979860snp) in seropositives. Seventy-five of these patients were found to be seropositive for HSV-1 and were subsequently enrolled in the study. Twenty-four of the enrolled patients also had a history of recurrent herpetic keratitis (HSK) associated with severe corneal scarring and visual acuity deterioration. Total DNA was isolated using blood samples. Two milliliters of peripheral venous blood were additionally collected from subjects with recurrent herpetic keratitis, in the acute phase of the disease, in order to determine folic acid and vitamin B12 levels. The results. A significant association was observed between recurrent HSK and two single nucleotide polymorphisms (SNP) of the IL28B genotype (CCrs12979860 and CTrs12979860, p<0.05). Our results show that all patients in the acute phase of the recurrent herpetic keratitis had lower B12 and folic acid sera levels. Conclusion. The results from our study indicate that the clinical manifestation of recurrent HSV- 1 infection may be related to IL28B gene polymorphism. HSV-1 virus reactivation may be associated with minimal vitamin B12 and folic acid deficiency during the latent phase of the disease, due to the epigenetic nature of the HSV-1 virus.en
dc.formatapplication/pdf
dc.languagesr
dc.publisherУниверзитет у Крагујевцу, Факултет медицинских наукаsr
dc.rightsopenAccessen
dc.sourceУниверзитет у Крагујевцуsr
dc.subjectgenske varijacije IL28Bsr
dc.subjectIL28B gene variationsen
dc.subjectrecurrent herpetic keratitisen
dc.subjectepigeneticsen
dc.subjectvitamin B12 and folic aciden
dc.subjectrekuretni herpetični keratitissr
dc.subjectepigenetikasr
dc.subjectvitamin B12 i folna kiselinasr
dc.titleUloga folne kiseline, vitamina B12 i genetičke varijacije IL28B gena u nastanku rekuretnog herpetičkog keratitisasr
dc.typedoctoralThesisen
dc.rights.licenseBY-NC-ND
dc.identifier.fulltexthttp://nardus.mpn.gov.rs/bitstream/id/66187/Disertacija.pdf
dc.identifier.fulltexthttp://nardus.mpn.gov.rs/bitstream/id/66188/Izvestaj_Borivoje_Savic_Medicina.pdf


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