20.500.12556/DKUM-61042 GENOTIPIZACIJA SLOVENSKIH BOLNIKOV Z REVMATOIDNIM ARTRITISOM ZA DNA POLIMORFIZME PREDHODNO POVEZANE Z BOLEZNIJO V ASOCIACIJSKIH ŠTUDIJAH V CELOTNEM GENOMU GENOTYPING OF SLOVENIAN PATIENTS WITH RHEUMATOID ARTHRITIS FOR DNA POLYMORPHISMS PREVIOUSLY ASSOCIATED WITH THE DISEASE IN GENOME WIDE ASSOCIATION STUDIES Revmatoidni artritis je kronična avtoimunska bolezen s kompleksno genetsko etiolologijo. Prizadene vse sklepne dele telesa. Študije so pokazale da poleg okoljskih dejavnikov k razvoju bolezni pomemben delež prispevajo tudi genetski dejavniki. Ocenjen prispevek dednega dejavnika je 60 %. V patogenezo bolezni je vpleteno veliko število polimorfizmov posameznega nukleotida (SNP). Namen magistrskega dela je ugotoviti ali so SNP-ji, ki so bili najbolj statistično značilni v GWA študijah statistično značilni tudi za slovenske bolnike z RA. V raziskavi smo izbrali rs1571878 (CCR6), rs7574865 (STAT4), rs909685 (SYNGR1), rs2476601 (PTPN22) in rs3087243 (CTLA4). Izvedli smo genotipizacijo s PCR-RFLP metodo in HRM metodo na 276 vzorcih bolnikov in 276 vzorcih zdravih kontrol. Rezultate smo analizirali s statistično analizo. Statistična analiza je pokazala povezavo med RA in SNP-jema rs2476601 (PTPN22) (p=0,000013) in rs3087243 (CTLA4) (p=0,002). Alel A za SNP rs2476601 zvišuje tveganje za nastanek RA. Za SNP rs3087243 ima alel G zaščitno vlogo proti nastanku RA. Rheumatoid arthritis is a chronic an autoimmune disease with a complex genetic etiololoy. It affects all joints of the body. Studies have shown that in addition to the environmental factors genetic factors also contribute an important proportion to the development of the disease. The estimated contribution of hereditary factors is 60%. However, it is known that a substantial number of single nucleotid polymorphisms (SNP) are involved in the pathogenesis of the disease. The aim of the master thesis was to find out whether are the most strongly associated SNP-s in the GWA studies also associated with the slovenian patients with RA. In this study, we have chosen rs1571878 (CCR6), rs7574865 (STAT4), rs909685 (SYNGR1), rs2476601 (PTPN22) and rs3087243 (CTLA4). We performed genotypization using PCR-RFLP method and HRM method in 276 samples of patients and 276 samples of healthy controls. Results have been analyzed with the statistical analysis. In the assignment we have confirmed associations between SNPs rs2476601 (PTPN22) (p=0,000013) and rs3087243 (CTLA4) (p=0.002). Allele A for SNP-rs2476601 increases the risk of developing RA. For SNP-rs3087243, allel G has a protective role in the development of RA. revmatoidni artritis asociacijske študije na celotnem genomu verižna reakcija s polimerazo polimorfizem dolžin celotnega genoma genotipizacija rheumatoid arthritis Genome Wide Association Studies Polymerase Chain Reaction Restriction Fragment Lenght Polymorphism genotyping true true false [D. Gselman] Slovenski jezik Angleški jezik Magistrsko delo/naloga 2016-07-17 16:38:48 2016-09-06 14:14:25 2022-06-25 03:07:21 2019-07-11 12:06:57 2016 0 Maribor 0 0000-00-00 NiDoloceno NiDoloceno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 575.22:616.72-002(043.2) 20298774 URN:SI:UM:DK:KNOD8NZW MAG_Gselman_Doroteja_2016.pdf MAG_Gselman_Doroteja_2016.pdf 1 9CAB6FA68BB61375F4D202666ACDA2F8 748035bcdd418fbc333d286430c5e8a2d70011180ad706dc82b6d5b87e89f755 43c9896d-7c0d-11eb-bb7a-00155d0001ca https://dk.um.si/Dokument.php?lang=slv&id=101909 Fakulteta za kemijo in kemijsko tehnologijo 0 0 0