Expression of genes involved in epigenetic modifications in patients with rheumatoid arthritis

Abstract

BackgroundRheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease, and evidence revealed that environmental and genetic factors are involved in RA pathogenesis. This study aimed to explore the balance between genes involved in DNA methylation and demethylation in the peripheral blood of patients with RA. MethodsIn this cross-sectional study, ninety RA patients and ninety-two age and sex-matched normal subjects (NS) were enrolled, and RA was confirmed by an expert rheumatologist based on clinical and laboratory data. In addition, the Rheumatoid arthritis severity scale (RASS) and disease activity score (DAS-28) were measured. According to the disease severity, RA patients were categorized into three groups (mild, moderate, and severe). Peripheral blood was collected from subjects, and the expression of ten-eleven translocation methylcytosine dioxygenase 1 (TET1), TET2, and TET3, as well as DNA methyltransferase 1 (DNMT1) genes, were evaluated using real-time polymerase chain reaction (RT-PCR) technique. Serum level of anti-cyclic citrullinated peptide (anti-CCP) antibody was measured by enzyme-linked immunosorbent assay (ELISA) technique. ResultsThis investigation showed that gene expression of TET1 and TET2 was significantly decreased in RA patients compared to NS. Gene expression of DNMT1 and TET3 was also down-regulated in RA patients compared to NS; however, the changes were not statistically significant. Moreover, the correlation matrix test demonstrated no significant association between some demographic and clinical data of RA patients with the expression of studied genes. ConclusionAccording to the findings of this study, the expression of TET1 and TET2 as regulators of inflammatory responses was remarkably reduced in RA patients compared to NS, and disease severity can affect the expression of these genes because the expression of the TET2 is significantly reduced in patients with moderate RA severity and it may lead to increase inflammatory responses and RA development.