Table 2.
Basic research studies showing specific changes in DNA methylation in patients with rheumatoid arthritis (RA).
| Study | Gene (s)/Region (s) Implicated | Main Results |
|---|---|---|
| [59] | Human leukocyte antigen (HLA)-DR-3 | DR-3 gene was differentially methylated in patients with RA. As a result, the expression of DR-3 protein was downregulated in synovium, thereby providing higher resistance to apoptosis in these cells |
| [60] | Interleukin 6 (IL6) | Lower methylation and subsequent higher expression of IL6 in peripheral blood mononuclear cells in patients with RA |
| [61] | C-X-C motif chemokine 12 (CXCL12) | CXCL12 gene was hypomethylated in patients with RA and the levels of CXCL12 were subsequently higher in these patients than in those with osteoarthritis, promoting activation of matrix metalloproteinases and joint destruction |
| [62] | Genome-wide studies comparing stromal fibroblast-like synoviocytes in patients with RA or osteoarthritis | Identification of ~2000 loci differentially methylated, including genes involved in immune response, migration, and cellular adhesion |
| [63] | Identification of 2 methylation clusters in the major histocompatibility complex (MHC) region associated with epigenetic risk for RA | The DNA methylation study sorted CD14+ monocytes of patients with RA and controls, finding 9 differential methylated sites located in the MHC region and suggesting that monocytes are more proximal to the pathogenic cell type |
| [64] | Interleukin 6 receptor (IL6R), calpain 8 (CAPN8), homeobox protein Hox-A11 (HOXA11), dipeptidyl-peptidase 4 (DPP4), and homeobox protein Hox-C4 (HOXC4) | The study showed hypomethylation of IL6R, CAPN8, and HOXA11, and hypermethylation of DPP4 and HOXC4, respectively, in the synovial fibroblasts of patients with RA |
| [65] | Dual specificity phosphatase 22 (DUSP22) and polypeptide N-acetylgalactosaminyltransferase 9 (GALNT9) | Multiple sites within DUSP22 and GALNT9 genes were consistently hypermethylated and hypomethylated, respectively, in T-lymphocytes from patients with RA |
| [66] | T-cell surface glycoprotein CD1c (CD1C), TNF superfamily member 10 (TNFSF10), parvin gamma (PARVG), nidogen 1 (NID1), dehydrogenase/reductase 12 (DHRS12), inositol-tetrakisphosphate 1-kinase (ITPK1), acyl-CoA synthetase family member 3 (ACSF3), and TNF receptor superfamily member 13C (TNFRSF13C) | Although there were differentially methylated genes in patients and control groups, the study showed similar patterns of epigenetic changes in B-lymphocytes from patients with RA or systemic lupus erythematosus |
| [67] | Poly (ADP-ribose) polymerase family member 9 (PARP9) | The study identified an interferon-inducible gene interaction network. The significance of PARP9 gene methylation and the resulting change in gene expression in the pathogenesis of RA was demonstrated. In addition, the ability of PARP9 gene to positively regulate interleukin 2, which stimulates various cells of the immune response, was revealed. |