| Abstract [eng] |
The aim of the study was to evaluate the associations of environmental, genetic and epigenetic factors (vitamin D level, periodontitis, vitamin D receptor gene (VDR) polymorphisms (BsmI, ApaI, FokI, TaqI), vitamin D pathway genes DNA methylation level) with rheumatoid arthritis (RA) disease activity, clinical course and determine the possible association of VDR gene polymorphisms and RA susceptibility. The study evaluated vitamin D (25(OH)D) deficiency prevalence in RA and control group subjects, its association with RA disease clinical parameters. For the first time in Lithuania, the distribution of VDR gene allele and genotype variants was evaluated in RA cases and healthy controls. The study data revealed differences of genetic diversity, contributed to the available knowledge on the prevalence of genetic polymorphisms in Lithuania and the possible influence on multifactorial vitamin D metabolism. Moreover, none of the previously published scientific articles has evaluated the methylation level of vitamin D signaling pathway genes in RA patients yet, which was also studied for the first time in this doctoral dissertation. Differentially methylated VDR, CYP24A1, and CYP2R1 gene promoter regions were identified and correlation analysis of variables was performed. This study supported the connection of the associations between genetic and epigenetic factors with RA clinical parameters, as well as vitamin D level. This doctoral dissertation evaluated the prevalence of potential risk factors – vitamin D deficiency and chronic periodontitis – in RA patients, thus establishing the reciprocity of these factors for the course of the disease, and providing practical clinical benefits for modulating arthritis. |
