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 Real-time feedback helps save energy and water
08.02.2017 | Otto-Friedrich-Universität Bamberg

nachricht The Great Unknown: Risk-Taking Behavior in Adolescents
19.01.2017 | Max-Planck-Institut für Bildungsforschung

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: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...

Im Focus: Dresdner scientists print tomorrow’s world

The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.

The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...

Im Focus: Mimicking nature's cellular architectures via 3-D printing

Research offers new level of control over the structure of 3-D printed materials

Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...

Im Focus: Three Magnetic States for Each Hole

Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".

Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

Positrons as a new tool for lithium ion battery research: Holes in the electrode

22.02.2017 | Power and Electrical Engineering

New insights into the information processing of motor neurons

22.02.2017 | Life Sciences

Healthy Hiking in Smart Socks

22.02.2017 | Innovative Products

VideoLinks
B2B-VideoLinks
More VideoLinks >>>