DNA methylation involved in development of rheumatoid arthritis
18 July 2012
Modification of DNA plays a key role in inflammation and joint
damage. A research team at the University of California, San Diego found
that epigenetic changes due to methylation of DNA are involved in the
progression of rheumatoid arthritis (RA).
Their study is published in the online edition of the
Annals of the Rheumatic Diseases.
DNA methylation is one example of epigenetic change, in which a
strand of DNA is modified after it is duplicated by adding a methyl
to any cytosine molecule (C) — one of the 4 main bases of DNA. This
is one of the methods used to regulate gene expression, and is often
abnormal in cancers and plays a role in organ development.
While DNA methylation of individual genes has been explored in
autoimmune diseases, this study represents a genome-wide evaluation
of the process in fibroblast-like synoviocytes (FLS), isolated from
the site of the disease in RA. FLS are cells that interact with the
immune cells in RA, an inflammatory disease in the joints that
damages cartilage, bone and soft tissues of the joint.
In this study, scientists isolated and evaluated genomic DNA from
28 cell lines. They looked at DNA methylation patterns in RA FLS and
compared them with FLS derived from normal individuals or patients
with non-inflammatory joint disease. The data showed that the FLS in
RA display a DNA methylome signature that distinguishes them from
osteoarthritis and normal FLS. These FLS possess differentially
methylated (DM) genes that are critical to cell trafficking,
inflammation and cell–extracellular matrix interactions.
“Genomics has rapidly advanced our understanding of
susceptibility and severity of rheumatoid arthritis,” said Gary
Firestein, professor in the Division of Rheumatology, Allergy and
Immunology at the University. “While many genetic associations have
been described in this disease, we also know that if one identical
twin develops RA that the other twin only has a 12 to 15% chance of
also getting the disease. This suggests that other factors are at
play – epigenetic influences.”
“We found that hypomethylation of individual genes was associated
with increased gene expression and occurred in multiple pathways
critical to inflammatory responses,” said Firestein, adding that
this led to their conclusion: Differentially methylated genes can
alter FLS gene expression and contribute to the pathogenesis of RA.