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Genetic Risk Factor For
Rheumatoid Arthritis, Lupus, Identified By Study
edited by Joint-Pain-Forum.com
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.
results appear in 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.
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."
form of the gene was present at a significantly higher frequency in RA
patient samples from the North American Rheumatoid Arthritis Consortium
(NARAC) as compared with controls. The scientists replicated that
result in two independent collections of RA cases and controls.
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.
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.
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."
www.Joint-Pain-Forum.com from original press release.
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.
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.
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.
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,
visit the NIAMS Web site at http://www.niams.nih.gov/.
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.
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.
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.
information about NIH and its programs, visit http://www.nih.gov/
Reference: Remmers E, et al. STAT4 and the risk of
rheumatoid arthritis and systemic lupus erythematosus. NEJM
Source: Ray Fleming
Institute of Arthritis and Musculoskeletal and Skin Diseases
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