Identification of genetic factors associated with Sjögren's syndrome

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dc.contributor.advisorSemsei, Imre
dc.contributor.authorMárka, Marietta
dc.contributor.departmentDE -- Orvos- és Egészségtudományi Centrum -- Általános Orvostudományi Kar -- III. sz. Belgyógyászati Klinikahu
dc.contributor.departmentElméleti orvostudományok doktori iskolahu
dc.date.accessioned2007-05-16T11:04:37Z
dc.date.available2007-05-16T11:04:37Z
dc.date.created2005
dc.description.abstractAutoimmune diseases have a very complex clinical picture, several factors may play a role in the onset of the autoimmune disease and the disease susceptibility such as genetic polymorphisms (e.g. interleukins), autoantibodies (antiRo/SSA, antiLa/SSB, etc.). AntiRo/SSA and antiLa/SSB autoantibodies are not only of diagnostic value but they may even play a role in the pathogenesis of several diseases. Ultraviolet (UV) radiation and the hormonal milieu are well-known cofactors in the pathogenesis of these diseases. The goal of our research was to study the possible alterations in mRNA levels of three different Ro antigens and that of two La species in transformed human keratinocytes (HaCaT cells) after UVB irradiation as well as after 17-β-estradiol treatment. The PCR technique was used to determine the mRNA levels of the Ro and La species after 24, 48, and 72 hours of irradiation. mRNA levels of calreticulin increased as a function of time after UV irradiation but mRNA levels of Ro 52 kDa and 60 kDa Ro mRNAs were unaltered. After treating the cells with 17-β-estradiol, there was no change observed in the levels of Ro mRNAs or La exon1 mRNA. The importance of alterations in the ratio of La exon1 to exon1’ is supported by the observations in patients with Sjögren’s syndrome, and our results strengthen their role in the pathogenesis of different autoimmune diseases. A further aim of our study was to investigate the frequency of the -1082 polymorphism of the interleukin-10 (IL-10) gene and soluble IL-10 levels in Hungarian Sjögren’s syndrome (Ss) patients. Samples were analyzed by the PCR-RFLP method and IL-10 plasma levels were assesed by a commercial ELISA assay. IL-10 plasma levels were higher in the primary Ss patients compared with healthy subjects. The elevated IL-10 phenotype of Ss patients was not associated with increased G allele frequency as reported earlier, while in the control group, we found higher IL-10 levels among the subjects who were carriers of the GG genotype as compared to the other two genotypes. Our data do not support some previous observations that indicated an association between deregulated IL-10 secretion in Ss and higher G allele frequency. However, our results clearly demonstrate that GG homozygosity is associated with elevated IL-10 levels in apparently healthy subjects, but this can not account for the IL-10 related specific disease features observed in Ss. Thus, other genetic factors contribute to the clinical spectrum of this heterogeneous disease at least in the Hungarian population.en
dc.description.bibliographyBibliogr.: p. 63-84hu
dc.description.degreeDissertation of doctor of philosophy (Ph.D.); University of Debrecen, Medical and Health Science Center, 3rd Department of Medicine, Molecular Biology Research Laboratory, 2005hu
dc.description.degreePhDhu_HU
dc.format.extent86, [25] pen
dc.format.extent164990 bytes
dc.format.extent149365 bytes
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dc.format.mimetypeapplication/pdf
dc.format.mimetypeapplication/pdf
dc.format.mimetypeapplication/pdf
dc.identifier.urihttp://hdl.handle.net/2437/2295
dc.languageenghu
dc.language.isohuen
dc.language.isoenen
dc.rightsA kéziratos egyetemi doktori (Ph.D.) értekezések csak a szerzői jogok maradéktalan tiszteletben tartásával használhatókhu
dc.titleIdentification of genetic factors associated with Sjögren's syndromeen
dc.title.subtitledissertation of doctor of philosophy (Ph.D.)en
dc.title.translatedSjörgen-szindrómában szerepet játszó genetikai faktorok vizsgálataen
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