Navigation Links
New Risk Gene for Rheumatoid Arthritis and Lupus Opens Door to More Effective Treatments
Date:9/6/2007

MANHASSET, N.Y., Sept. 6 /PRNewswire-USNewswire/ -- Scientists at The Feinstein Institute for Medical Research have identified a critical gene that increases a person's risk for rheumatoid arthritis and systemic lupus erythematosus, and may be involved with other autoimmune diseases.

The genetic link, described in the September 6th issue of the New England Journal of Medicine, was a collaborative effort led by Peter K. Gregersen, MD, head of The Feinstein Institute's Robert S. Boas Center for Genomics & Human Genetics. A decade ago, Dr. Gregersen helped bring together scientists from a dozen institutes to pool patients and add strength in numbers as they collectively hunt for genes. More recently, the North American Rheumatoid Arthritis Consortium (NARAC) studied a region identified on chromosome 2 in previous linkage studies conducted by the same team. In the latest study, they analyzed DNA from 2,500 patients with rheumatoid arthritis (RA) or lupus. Genetic mapping enabled them to identify STAT4 as a culprit in susceptibility to both diseases.

"This work required the collection and genotyping of thousands of RA and lupus patients and volunteers, a task that would have been difficult to accomplish without the strong partnerships we forged," said Stephen I. Katz, MD, PhD, director of the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS). The federal institute has supported NARAC since its inception.

"Identifying STAT4 as the relevant gene on chromosome 2 is very exciting," added Elaine Remmers, PhD, a lead author in the NEJM study on STAT4 and a staff scientist in the NIAMS's Genetics and Genomics Branch. "We now are faced with trying to figure out how this variant of STAT4 increases a person's risk."

About 22 percent of people in the United States inherit this particular form of STAT4. Having this variant of STAT4 confers a 30 percent increased risk for developing rheumatoid arthritis. People with two copies of STAT4 have a 60 percent increased risk, Dr. Gregersen said. Rheumatoid arthritis is a painful inflammatory condition of the joints. It is an autoimmune disease, which means the body's immune system recognizes a product in the lining of the joint as foreign and wages an attack. Patients with lupus, also an autoimmune disease, have about double the risk compared to people without this variant of STAT4.

In a companion study by Dr. Gregersen and his colleagues, STAT4 popped up as an important risk gene in a population of patients in Korea. This paper is published this month in Molecular Medicine.

One percent of people will develop rheumatoid arthritis. There are probably dozens of genes, perhaps more, involved in triggering complex diseases like rheumatoid arthritis.

"Identifying this risk gene is important because it points us in the right direction," said Dr. Gregersen, who also just completed a whole genome-wide association study of rheumatoid arthritis that will appear later this month in the NEJM. The study is online as of September 6th with an accompanying editorial. In this paper, the scientists identified another risk gene -- TRAF1-C5.

"The identification of these two new autoimmunity genes has profound significance for our understanding of these complex diseases and our ability to develop more specific diagnostic tests and therapies," said Lindsey Criswell, MD, PhD, professor of medicine at UCSF and a co-investigator on both studies.

A lot is known about the STAT4 gene and the protein it makes. STAT4 is a signaling molecule that mediates the effects of immune system cytokines such as IL12 and some types of interferon. STAT4 controls the differentiation of T- cells into TH1 cells and may contribute to the development of TH17 cells, both of which seem to have a role in maintaining chronic inflammation in the body.

Inhibiting STAT4 can prevent or ameliorate arthritis in animal models of rheumatoid arthritis, suggesting that STAT4 could be a target for new therapies. The discovery of STAT4 can ultimately help scientists unravel the triggers for the disease, help in the development of a test to confirm a diagnosis and perhaps even help predict who will respond to treatments.

The NARAC and collaborators at Celera Diagnostics previously identified PTPN22 as another risk gene in 2004. PTPN22 influences the "trigger point" for activation of T-cells -- immune cells normally called on to wage battle against infection. In autoimmune diseases like rheumatoid arthritis, PTPN22 appears to put people at higher risk of a wayward T-cell response. Dr. Gregersen said that the two genes -- PTPN22 and STAT4 -- appear to work independently to increase the risk for rheumatoid arthritis.

These are the first RA genes to be discovered since the 1980s when scientists reported detailed association with genetic variants in the HLA region known as the "shared epitope," work for which Dr. Gregersen is still widely recognized. The key to the new genetic discoveries, Dr. Gregersen said, is to have "more patients and controls. With higher numbers of volunteers, we will have more power to pull out additional new genes and figure out what they do in triggering these diseases. Continued international collaboration with colleagues at the Karolinska Institute in Stockholm will be critical for these efforts."

In addition to Drs. Gregersen, Criswell and Remmers, the NARAC investigators on the STAT4 study include Christopher Amos, PhD, of The University of Texas M.D. Anderson Cancer Center; Daniel Kastner MD, PhD, of NIAMS's Genetics and Genomic Branch; Michael F. Seldin MD, PhD, of the University of California, Davis; and Robert M. Plenge, MD, PhD, of the Brigham and Women's Hospital. Timothy W. Behrens, MD, senior director of immunology, tissue growth & repair at Genentech, Inc. was a key collaborator on the lupus research.

The NARAC team is also part of the whole genome association study to be published later this month in the NEJM. Other collaborators on this study include Lars Klareskog of the Karolinska Institute; Mark Seielstad of the Genome Institute of Singapore; and John Carulli, PhD, and Evan Beckman, MD, of Biogen Idec in Cambridge, Ma.

Headquartered in Manhasset, NY, The Feinstein Institute for Medical Research is home to international scientific leaders in Parkinson's disease, Alzheimer's disease, psychiatric disorders, rheumatoid arthritis, lupus, sepsis, inflammatory bowel disease, diabetes, human genetics, leukemia, lymphoma, neuroimmunology, and medicinal chemistry. The Feinstein Institute, part of the North Shore-LIJ Health System, ranks in the top 6th percentile of all National Institutes of Health grants awarded to research centers. Feinstein researchers are developing new drugs and drug targets, and producing results where science meets the patient. For more information, please visit http://www.FeinsteinInstitute.org or http://feinsteininstitute.typepad.com/feinsteinweblog/

Contact: Jamie Talan

516-562-1232


'/>"/>
SOURCE The Feinstein Institute for Medical Research
Copyright©2007 PR Newswire.
All rights reserved

Related medicine technology :

1. Actemra (tocilizumab) Third Phase III Study Results Show Significant Improvement in Symptoms of Patients with Rheumatoid Arthritis
2. Three Studies Suggest Abbotts Humira (adalimumab) May Improve Work Productivity in Patients with Rheumatoid Arthritis
3. GlaxoSmithKline and Genmab Present Positive Phase II Results With ofatumumab in Patients With Rheumatoid Arthritis (RA)
4. Actemra (tocilizumab) Significantly Improves Symptoms of Rheumatoid Arthritis Compared to a Current Standard of Care
5. Anti-TNF Golimumab Continues to Show Promise in Phase II Rheumatoid Arthritis Study
6. Cimzia Effective in Reducing Signs and Symptoms of Rheumatoid Arthritis
7. Three New Drugs Mark New Era in Rheumatoid Arthritis Treatment
8. Enbrel Safety Data for up to Eight Years in Patients with Juvenile Rheumatoid Arthritis Being Presented at EULAR
9. New Data Confirms Significant Improvement of Disease Signs and Symptoms in Patients with Rheumatoid Arthritis
10. New Data on Genmab and GlaxoSmithKlines Ofatumumab: Phase II Study in Rheumatoid Arthritis to be Presented at EULAR
11. Rigel Provides Clinical Update of R788 Phase 2 Trials in ITP, Rheumatoid Arthritis and Lymphoma
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:6/26/2016)... One of Australia,s successful biotechnology ... a new biotechnology company, Noxopharm Limited [ABN 50 608 966 123] ... to list on the ASX. Noxopharm is a clinic-ready ... a Phase 1 clinical study later this year. ... the biggest problems facing cancer patients - the ability of cancers ...
(Date:6/26/2016)... Jazz Pharmaceuticals plc (Nasdaq: JAZZ ... Antitrust Improvements Act of 1976, as amended ("HSR"), with ... ("Celator"; Nasdaq: CPXX ) expired effective June ... As previously announced on May 31, 2016, Jazz ... under which Jazz Pharmaceuticals has commenced a tender offer ...
(Date:6/26/2016)... OTTAWA, Ontario , June 27, 2016  VMS ... the Company,s Board will take whatever measures required to ... the Company,s stock which is currently listed on the ... S Wexler, Company Chairman and CEO, "We are seeing ... be difficult to understand, not only by the Company, ...
Breaking Medicine Technology:
(Date:6/26/2016)... Orion, Clarkston, Michigan (PRWEB) , ... June 26, ... ... with respect to fertility once they have been diagnosed with endometriosis. These women ... intercourse but they also require a comprehensive approach that can help for preservation ...
(Date:6/25/2016)... ... ... First Choice Emergency Room , the largest network of independent freestanding ... of its new Mesquite-Samuell Farm facility. , “We are pleased to announce Dr. ... James M. Muzzarelli, Executive Medical Director of First Choice Emergency Room. , Dr. ...
(Date:6/24/2016)... ... ... A recent article published June 14 on E Online details ... to state that individuals are now more comfortable seeking to undergo not only the ... and cheek reduction. The Los Angeles area medical group, Beverly Hills Physicians (BHP) notes ...
(Date:6/24/2016)... ... June 24, 2016 , ... Global law firm Greenberg Traurig, P.A. ... The attorneys chosen by their peers for this recognition are considered among the top ... Shareholders received special honors as members of this year’s Legal Elite Hall of Fame: ...
(Date:6/24/2016)... ... June 24, 2016 , ... EB Medicine presented ... in Emergency Medicine conference in Ponte Vedra Beach, FL. The awards honor the ... Emergency Medicine Practice and Pediatric Emergency Medicine Practice. , “With this award, ...
Breaking Medicine News(10 mins):