Featured Research

from universities, journals, and other organizations

Scientists Discover Genetic Marker Responsible For Two-fold Increase In Risk Of Rheumatoid Arthritis

Date:
June 24, 2004
Source:
North Shore-Long Island Jewish Health System
Summary:
A team of researchers has discovered a genetic variation that doubles the risk for rheumatoid arthritis (RA). The variation, referred to as a single nucleotide polymorphism (SNP, pronounced "snip"), is present in about 28 percent of individuals with rheumatoid arthritis and 17 percent of the general population.

MANHASSET, NY – A team of researchers has discovered a genetic variation that doubles the risk for rheumatoid arthritis (RA). The variation, referred to as a single nucleotide polymorphism (SNP, pronounced "snip"), is present in about 28 percent of individuals with rheumatoid arthritis and 17 percent of the general population. This discovery resulted from a collaboration between scientists from the North American Rheumatoid Arthritis Consortium (NARAC), led by Peter K. Gregersen, MD, of the North Shore-Long Island Jewish Research Institute in Manhasset, NY, Celera Diagnostics and Genomics Collaborative, Inc. The team's findings are being published in the August 2004 issue of the American Journal of Human Genetics.

"This is an important discovery, really a major genetic variant identified in a U.S. study that clearly seems to be involved in rheumatoid arthritis," said Stephen I. Katz, MD, PhD, director of the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), the lead agency at the National Institutes of Health (NIH) that supports NARAC.

While scientists still do not know the exact cause of RA, they do know it is an autoimmune disease in which the body's natural immune system does not function properly and attacks its own healthy joint tissues. This causes inflammation and subsequent joint damage.

The SNP they linked to RA is located in a gene that codes for an enzyme (called PTPN22) that is known to be involved in controlling the activation of immune cells called T cells. Under normal conditions, the enzyme works as a "negative regulator" --- meaning it inactivates a specific signaling molecule, which in turn interrupts the communication lines and keeps immune cells from becoming overactive. In cases where the SNP is present in one or both copies of an individual's genes for this enzyme, the team found that the negative regulation by this enzyme appears to be inefficient, so that T cells and other immune cells are hyperresponsive, causing increased inflammation and tissue damage.

"This is not an abnormal gene," said Dr. Gregersen. "It is present in a substantial fraction of the normal population, so it's probably there for a good reason. It may, in fact, help defend against infection." When it comes to the genetics of complex diseases, context is everything. According to Dr. Gregersen, a genetic variant in the setting of certain environments and in the presence of other genes may have harmful effects, whereas the same genetic variant may have beneficial effects in another genetic and environmental context. "So this particular genetic variation may have contributed to the survival of our ancestors. The price we have to pay for that, however, is that some people are modestly predisposed to developing rheumatoid arthritis."

Using state-of-the-art technology developed by Celera Diagnostics, Ann B. Begovich, PhD, director of inflammation at Celera Diagnostics, and her team discovered the PTPN22 association. The technology allowed them -- in a short period of time -- to look at tens of thousands of SNPs in thousands of DNA samples from subjects with RA as well as normal control subjects. The majority of the DNA samples analyzed in this study were carefully collected from families with RA who contributed to the NARAC project. Genomics Collaborative, Inc. provided additional samples.

"This collaboration has enabled us to make a significant contribution to a very complex genetic problem in a relatively short period of time, something that can only be achieved with a team effort," said Dr. Begovich.

The Arthritis Foundation has been an important supporter of NARAC. "This critical discovery is an illustration of the power of public-private partnerships to solve complex issues," said John H. Klippel, MD, the foundation's president and CEO.

Research has previously shown that autoimmune diseases such as type 1 diabetes, lupus and thyroid disease tend to group in families, but there has been no previous direct genetic connection to explain the phenomenon. Earlier this year, a study published in Nature Genetics linked this same SNP with type 1 diabetes. Subsequent unpublished research by Dr. Gregersen and his colleagues indicates that this particular gene variant may also increase risk for other autoimmune diseases, such as systemic lupus and autoimmune thyroid disease, as well as type 1 diabetes.

"NIH has provided strong scientific and financial support for the North American Rheumatoid Arthritis Consortium over many years, and we are now beginning to see the fruits of this investment," said Dr. Katz. "I expect this discovery will spin off many more advances in the field." In addition to NIAMS, the National Institute of Allergy and Infectious Diseases and the Office of Research on Women's Health at the NIH also support NARAC.

###

Note to Editors: The full text of this journal article to appear in the August 2004 print issue of American Journal of Human Genetics is currently available online from http://www.journals.uchicago.edu/AJHG.

"A Missense Single-Nucleotide Polymorphism in a Gene Encoding a Protein Tyrosine Phosphatase (PTPN22) Is Associated with Rheumatoid Arthritis"


Story Source:

The above story is based on materials provided by North Shore-Long Island Jewish Health System. Note: Materials may be edited for content and length.


Cite This Page:

North Shore-Long Island Jewish Health System. "Scientists Discover Genetic Marker Responsible For Two-fold Increase In Risk Of Rheumatoid Arthritis." ScienceDaily. ScienceDaily, 24 June 2004. <www.sciencedaily.com/releases/2004/06/040624091949.htm>.
North Shore-Long Island Jewish Health System. (2004, June 24). Scientists Discover Genetic Marker Responsible For Two-fold Increase In Risk Of Rheumatoid Arthritis. ScienceDaily. Retrieved August 23, 2014 from www.sciencedaily.com/releases/2004/06/040624091949.htm
North Shore-Long Island Jewish Health System. "Scientists Discover Genetic Marker Responsible For Two-fold Increase In Risk Of Rheumatoid Arthritis." ScienceDaily. www.sciencedaily.com/releases/2004/06/040624091949.htm (accessed August 23, 2014).

Share This




More Health & Medicine News

Saturday, August 23, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Drug Used To Treat 'Ebola's Cousin' Shows Promise

Drug Used To Treat 'Ebola's Cousin' Shows Promise

Newsy (Aug. 21, 2014) An experimental drug used to treat Marburg virus in rhesus monkeys could give new insight into a similar treatment for Ebola. Video provided by Newsy
Powered by NewsLook.com
Two US Ebola Patients Leave Hospital Free of the Disease

Two US Ebola Patients Leave Hospital Free of the Disease

AFP (Aug. 21, 2014) Two American missionaries who were sickened with Ebola while working in Liberia and were treated with an experimental drug are doing better and have left the hospital, doctors say on August 21, 2014. Duration: 01:05 Video provided by AFP
Powered by NewsLook.com
Cadavers, a Teen, and a Medical School Dream

Cadavers, a Teen, and a Medical School Dream

AP (Aug. 21, 2014) Contains graphic content. He's only 17. But Johntrell Bowles has wanted to be a doctor from a young age, despite the odds against him. He was recently the youngest participant in a cadaver program at the Indiana University NW medical school. (Aug. 21) Video provided by AP
Powered by NewsLook.com
American Ebola Patients Released: What Cured Them?

American Ebola Patients Released: What Cured Them?

Newsy (Aug. 21, 2014) It's unclear whether the American Ebola patients' recoveries can be attributed to an experimental drug or early detection and good medical care. 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