DNA methylome signature in rheumatoid arthritis

Abstract

Epigenetics such as DNA methylation can potentially influence disease susceptibility and severity. While methylation of individual genes has been explored in autoimmunity, no systematic analyses have been reported. We performed an unbiased genome-wide evaluation of DNA methylation in fibroblast-like synoviocytes (FLS) isolated from rheumatoid arthritis (RA) synovium. Using the Infinium HumanMethy-lation450 BeadChip, cluster analysis of the methylation state was performed on 476,331 CpG loci. RA and control FLS unexpectedly segregated into separate groups based on DNA methylation. Hypomethylated loci were identified in key genes relevant to R. A., such as CHI3L1, CASP1, and WISP3. Hypomethylated genes was associated with increased gene expression. Hypomethylation was increased in multiple pathways related to cell migration, including focal adhesion, cell adhesion, and extracellular matrix interactions. These pathways could contribute to migration of synoviocytes from the synovium to the surface of cartilage and other joints. DNA methylation of critical genes suggests that RA FLS are imprinted and implicate non-DNA encoding contributions to synovitis and joint damage. © 2012, The Japan Society for Clinical Immunology. All rights reserved.