Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Study identifies genetic risk factor for rheumatoid arthritis, lupus

10.09.2007
A genetic variation has been identified that increases the risk of two chronic, autoimmune inflammatory diseases: rheumatoid arthritis (RA) and systemic lupus erythematosus (lupus).

These research findings result from a long-time collaboration between the Intramural Research Program (IRP) of the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) and other organizations. NIAMS is part of the National Institutes of Health.

These results appear in the Sept. 6 issue of the New England Journal of Medicine.

"Although both diseases are believed to have a strong genetic component, identifying the relevant genes has been extremely difficult," says study coauthor Elaine Remmers, Ph.D., of the Genetics and Genomics Branch of the Intramural Research Program at the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Dr. Remmers and her colleagues tested variants within 13 candidate genes located in a region of chromosome 2, which they had previously linked with RA, for association with disease in large collections of RA and lupus patients and controls. Among the variants were several disease-associated single nucleotide polymorphisms (SNPs) — small differences in DNA sequence that represent the most common genetic variations between individuals — in a large segment of the STAT4 gene. The STAT4 gene encodes a protein that plays an important role in the regulation and activation of certain cells of the immune system.

"It may be too early to predict the impact of identifying the STAT4 gene as a susceptibility locus for rheumatoid arthritis — whether the presence of the variant and others will serve as a predictor of disease, disease outcome or response to therapy," says coauthor and NARAC principal investigator Peter K. Gregersen, M.D., of The Feinstein Institute for Medical Research, part of the North Shore Long Island Jewish Health System, in Manhasset, N.Y. "It also remains to be found whether the STAT4 pathway plays such a crucial role in RA and lupus that new therapies targeting this pathway would be effective in these and perhaps other autoimmune diseases."

One variant form of the gene was present at a significantly higher frequency in RA patient samples from the North American Rheumatoid Arthritis Consortium (NARAC)[1] as compared with controls. The scientists replicated that result in two independent collections of RA cases and controls.

The researchers also found that the same variant of the STAT4 gene was even more strongly linked with lupus in three independent collections of patients and controls. Frequency data on the genetic profiles of the patients and controls suggest that individuals who carry two copies of the disease-risk variant form of the STAT4 gene have a 60 percent increased risk for RA and more than double the risk for lupus compared with people who carry no copies of the variant form. The research also suggests a shared disease pathway for RA and lupus.

"For this complex disease, rheumatoid arthritis, this is the first instance of a genetic linkage study leading to a chromosomal location, which then, in a genetic association study, identified a disease susceptibility gene," says Dr. Gregersen.

The study's success, according to NIAMS Director Stephen I. Katz, M.D., Ph.D., can be attributed in part to the uncommon and longstanding collaboration between NIAMS intramural researchers and other scientists the Institute supports around the country. "This work required the collection and genotyping of thousands of RA and lupus cases and controls, a task that would have been difficult to accomplish without the strong partnerships we forged," he says. NARAC was established 10 years ago by Dr. Gregersen, NIAMS Clinical Director and Genetics and Genomics Branch Chief Daniel Kastner, M.D., Ph.D., and investigators at several academic health centers to facilitate the collection and analysis of RA genetic samples.

Adds Dr. Remmers, "Although we do not yet know precisely how the disease-associated variant of the STAT4 gene increases the risk for developing RA or lupus, it is very exciting to know that this gene plays a fundamental role in these important autoimmune diseases."

Both RA and lupus are considered autoimmune diseases, or diseases in which the body’s immune system attacks healthy tissue. In RA, the immune system attacks the linings of the joints and sometimes other organs. In lupus, it attacks the internal organs, joints and skin. If not well controlled, both diseases can lead to significant disability.

Additional grant support for this research was provided by the National Institute of Allergy and Infectious Diseases, the National Center for Research Resources, the Rosalind Russell Medical Research Center for Arthritis, and the Kirkland Scholar Award. The studies were carried out, in part, at the General Clinical Research Centers at Moffitt Hospital of the University of California San Francisco and at The Feinstein Institute for Medical Research, with funds provided by the National Center for Research Resources and the U.S. Public Health Service.

Other contributors included the Arthritis Foundation, Biogen Idec, Inc., the Boas Family, the Broad Institute of Harvard University and the Massachusetts Institute of Technology, the Eileen Ludwig Greenland Center for Rheumatoid Arthritis, Hanyang University College of Medicine, Genentech, Inc., the Karolinska Institutet, the NIAMS Intramural Research Program, the University of California Davis, and the University of Texas M.D. Anderson Cancer Center.

The mission of the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), a part of the Department of Health and Human Services' National Institutes of Health, is to support research into the causes, treatment and prevention of arthritis and musculoskeletal and skin diseases; the training of basic and clinical scientists to carry out this research; and the dissemination of information on research progress in these diseases. For more information about NIAMS, call the information clearinghouse at (301) 495-4484 or (877) 22-NIAMS (free call) or visit the NIAMS Web site at http://www.niams.nih.gov.

The National Institute of Allergy and Infectious Diseases (NIAID) conducts and supports basic and applied research to better understand, treat, and ultimately prevent infectious, immunologic, and allergic diseases.

The National Center for Research Resources (NCRR) provides clinical and translational researchers with the training and tools they need to understand, detect, treat, and prevent a wide range of diseases.

The National Institutes of Health (NIH) — The Nation's Medical Research Agency — includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. It is the primary federal agency for conducting and supporting basic, clinical and translational medical research, and it investigates the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.

Reference: Remmers E, et al. STAT4 and the risk of rheumatoid arthritis and systemic lupus erythematosus. NEJM 2007;357(10):13-22.

Ray Fleming | EurekAlert!
Further information:
http://www.niams.nih.gov

More articles from Studies and Analyses:

nachricht Innovative genetic tests for children with developmental disorders and epilepsy
11.07.2018 | Christian-Albrechts-Universität zu Kiel

nachricht Oxygen loss in the coastal Baltic Sea is “unprecedentedly severe”
05.07.2018 | European Geosciences Union

All articles from Studies and Analyses >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: First evidence on the source of extragalactic particles

For the first time ever, scientists have determined the cosmic origin of highest-energy neutrinos. A research group led by IceCube scientist Elisa Resconi, spokesperson of the Collaborative Research Center SFB1258 at the Technical University of Munich (TUM), provides an important piece of evidence that the particles detected by the IceCube neutrino telescope at the South Pole originate from a galaxy four billion light-years away from Earth.

To rule out other origins with certainty, the team led by neutrino physicist Elisa Resconi from the Technical University of Munich and multi-wavelength...

Im Focus: Magnetic vortices: Two independent magnetic skyrmion phases discovered in a single material

For the first time a team of researchers have discovered two different phases of magnetic skyrmions in a single material. Physicists of the Technical Universities of Munich and Dresden and the University of Cologne can now better study and understand the properties of these magnetic structures, which are important for both basic research and applications.

Whirlpools are an everyday experience in a bath tub: When the water is drained a circular vortex is formed. Typically, such whirls are rather stable. Similar...

Im Focus: Breaking the bond: To take part or not?

Physicists working with Roland Wester at the University of Innsbruck have investigated if and how chemical reactions can be influenced by targeted vibrational excitation of the reactants. They were able to demonstrate that excitation with a laser beam does not affect the efficiency of a chemical exchange reaction and that the excited molecular group acts only as a spectator in the reaction.

A frequently used reaction in organic chemistry is nucleophilic substitution. It plays, for example, an important role in in the synthesis of new chemical...

Im Focus: New 2D Spectroscopy Methods

Optical spectroscopy allows investigating the energy structure and dynamic properties of complex quantum systems. Researchers from the University of Würzburg present two new approaches of coherent two-dimensional spectroscopy.

"Put an excitation into the system and observe how it evolves." According to physicist Professor Tobias Brixner, this is the credo of optical spectroscopy....

Im Focus: Chemical reactions in the light of ultrashort X-ray pulses from free-electron lasers

Ultra-short, high-intensity X-ray flashes open the door to the foundations of chemical reactions. Free-electron lasers generate these kinds of pulses, but there is a catch: the pulses vary in duration and energy. An international research team has now presented a solution: Using a ring of 16 detectors and a circularly polarized laser beam, they can determine both factors with attosecond accuracy.

Free-electron lasers (FELs) generate extremely short and intense X-ray flashes. Researchers can use these flashes to resolve structures with diameters on the...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Leading experts in Diabetes, Metabolism and Biomedical Engineering discuss Precision Medicine

13.07.2018 | Event News

Conference on Laser Polishing – LaP: Fine Tuning for Surfaces

12.07.2018 | Event News

11th European Wood-based Panel Symposium 2018: Meeting point for the wood-based materials industry

03.07.2018 | Event News

 
Latest News

Leading experts in Diabetes, Metabolism and Biomedical Engineering discuss Precision Medicine

13.07.2018 | Event News

Research finds new molecular structures in boron-based nanoclusters

13.07.2018 | Materials Sciences

Algae Have Land Genes

13.07.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>