Featured Research

from universities, journals, and other organizations

Epigenetics alters genes in rheumatoid arthritis

Date:
July 3, 2012
Source:
University of California - San Diego
Summary:
Researchers have investigated a mechanism usually implicated in cancer and in fetal development, called DNA methylation, in the progression of rheumatoid arthritis. They found that epigenetic changes due to methylation play a key role in altering genes that could potentially contribute to inflammation and joint damage.

In this artist's rendering, a DNA molecule is methylated on both strands at the center cytosine. DNA methylation plays an important role in epigenetic gene regulation, and is involved in both normal development and in cancer.
Credit: UC San Diego School of Medicine

It's not just our DNA that makes us susceptible to disease and influences its impact and outcome. Scientists are beginning to realize more and more that important changes in genes that are unrelated to changes in the DNA sequence itself -- a field of study known as epigenetics -- are equally influential.

A research team at the University of California, San Diego -- led by Gary S. Firestein, professor in the Division of Rheumatology, Allergy and Immunology at UC San Diego School of Medicine -- investigated a mechanism usually implicated in cancer and in fetal development, called DNA methylation, in the progression of rheumatoid arthritis (RA). They found that epigenetic changes due to methylation play a key role in altering genes that could potentially contribute to inflammation and joint damage. Their study is currently published in the online edition of the Annals of the Rheumatic Diseases.

"Genomics has rapidly advanced our understanding of susceptibility and severity of rheumatoid arthritis," said Firestein. "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 percent chance of also getting the disease. This suggests that other factors are at play -- epigenetic influences."

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.

"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.

Additional contributors include Kazuhisa Nakano and David L. Boyle, UCSD Department of Medicine; and John W. Whitaker and Wei Wang, UCSD Department of Chemistry and Biochemistry.

This project was supported by grant number UL1RR031980 from the National Institutes of Health's National Center for Advancing Translational Science.

NexDx, Inc. licensed the technology from UC San Diego and provided informatics support for this study. Gary S. Firestein and Wei Wang are on the Scientific Advisory Board of NexDx, Inc.


Story Source:

The above story is based on materials provided by University of California - San Diego. Note: Materials may be edited for content and length.


Journal Reference:

  1. K. Nakano, J. W. Whitaker, D. L. Boyle, W. Wang, G. S. Firestein. DNA methylome signature in rheumatoid arthritis. Annals of the Rheumatic Diseases, 2012; DOI: 10.1136/annrheumdis-2012-201526

Cite This Page:

University of California - San Diego. "Epigenetics alters genes in rheumatoid arthritis." ScienceDaily. ScienceDaily, 3 July 2012. <www.sciencedaily.com/releases/2012/07/120703172549.htm>.
University of California - San Diego. (2012, July 3). Epigenetics alters genes in rheumatoid arthritis. ScienceDaily. Retrieved April 16, 2014 from www.sciencedaily.com/releases/2012/07/120703172549.htm
University of California - San Diego. "Epigenetics alters genes in rheumatoid arthritis." ScienceDaily. www.sciencedaily.com/releases/2012/07/120703172549.htm (accessed April 16, 2014).

Share This



More Health & Medicine News

Wednesday, April 16, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Ebola Outbreak Now Linked To 121 Deaths

Ebola Outbreak Now Linked To 121 Deaths

Newsy (Apr. 15, 2014) The ebola virus outbreak in West Africa is now linked to 121 deaths. Health officials fear the virus will continue to spread in urban areas. Video provided by Newsy
Powered by NewsLook.com
Cognitive Function: Is It All Downhill From Age 24?

Cognitive Function: Is It All Downhill From Age 24?

Newsy (Apr. 15, 2014) A new study out of Canada says cognitive motor performance begins deteriorating around age 24. Video provided by Newsy
Powered by NewsLook.com
How Mt. Everest Helped Scientists Research Diabetes

How Mt. Everest Helped Scientists Research Diabetes

Newsy (Apr. 15, 2014) British researchers were able to use Mount Everest's low altitudes to study insulin resistance. They hope to find ways to treat diabetes. Video provided by Newsy
Powered by NewsLook.com
Carpenter's Injury Leads To Hundreds Of 3-D-Printed Hands

Carpenter's Injury Leads To Hundreds Of 3-D-Printed Hands

Newsy (Apr. 14, 2014) Richard van As lost all fingers on his right hand in a woodworking accident. Now, he's used the incident to create a prosthetic to help hundreds. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins