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That Increase Rheumatoid Arthritis Risk Identified By Researchers
edited by Joint-Pain-Forum.com
Researchers in the United States and Sweden have identified a genetic region
associated with increased risk of rheumatoid arthritis (RA), a chronic and
debilitating inflammatory disease of the joints that affects an estimated 2.1
million Americans. The U.S. arm of the study involved a long-time collaboration
between intramural researchers of the National Institute of Arthritis and
Musculoskeletal and Skin Diseases (NIAMS) and other organizations. NIAMS is one
of 27 institutes and centers at the National Institutes of Health. The results
appeared in the New England Journal of Medicine.
relatively new genome-wide association approach -- which makes it possible to
analyze between 300,000 and 500,000 single nucleotide polymorphisms (SNPs, or
small differences in DNA that are distributed throughout a person's genetic
code) -- researchers in both countries searched for genetic differences in blood
samples from people with RA compared to controls. The U.S. group compared 908
samples from patients provided by the North American Rheumatoid Arthritis
Consortium (NARAC) -- a group of investigators working together to identify the
genetic factors that contribute to RA -- with those from 1,282 people without RA
(controls). The Swedish group compared 676 samples from the Swedish
Epidemiological Investigation of Rheumatoid Arthritis (EIRA) with 673 controls.
Both groups' searches led them to a region of chromosome 9 containing
two genes relevant to chronic inflammation: TRAF1 (encoding tumor necrosis
factor receptor-associated factor 1) and C5 (encoding complement component 5).
"The whole-genome screening method lets us identify genes that
contribute to disease-susceptibility without imposing our preconceived notions
of the disease. We expected to come up with something new," says Elaine F.
Remmers, Ph.D., of the Genetics and Genomics Branch of the NIAMS Intramural
Research Program and an author of the study. "We were thrilled to find out that
TRAF1-C5 showed association not only in the samples that we did with NARAC but
also independently in the Swedish group. By combining our information, we were
able to make a much stronger case [for a TRAF1-C5 association]. The combined
evidence was pretty impressive."
Remmers says the TRAF1-C5 region was
the third of three major susceptibility chromosomal regions for RA identified by
their whole genome screen. The first two, HLA-DRB1 and PTPN22, had already been
She says that it's not yet known how the genes in the
TRAF1-C5 region influence RA risk. Nor can scientists say which of the two genes
is causing the disease. "Actually, both genes are very interesting candidates,"
she says. "They both control inflammatory processes that really are relevant for
the disease, so we could easily envision either of them playing a role -- or
The hope is that by learning more about the genes and their role
in the disease, scientists may find clues to influencing treatment of the
disease. "We are hoping that we will find variants in either of the genes that
will lead us to new targets for therapy. Once we understand how the
RA-associated variants work, we may be able interfere with the pathways the
variants are influencing and either prevent the disease or block its
According to coauthor Daniel Kastner, M.D., Ph.D., NIAMS
clinical director and chief of the NIAMS Genetics and Genomics Branch, "The
success of the study can be attributed in part to the productive, longstanding
collaboration between NIAMS intramural researchers and other scientists that the
Institute supports around the country." NARAC was established 10 years ago by
coauthor Peter K. Gregersen, M.D., at the Feinstein Institute for Medical
Research, the North Shore Long Island Jewish Health System, in order to
facilitate the collection and analysis of RA genetic samples. Kastner was also a
key early member of the NARAC, as were many other investigators at several
academic health centers across the United States.
www.Joint-Pain-Forum.com from original press release.
In addition to NIAMS, other support for the U.S. study came from the National
Center for Research Resources, the Arthritis Foundation, grants from the Boas
Family and the Eileen Ludwig Greenland Center for Rheumatoid Arthritis
(Feinstein Institute for Medical Research), the Rosalind Russell Medical
Research Center for Arthritis and the Kirkland Scholar Award (University of
California, San Francisco).
Support for the Swedish arm of the study
came from the Swedish Medical Research Council, the Swedish Council for Working
Life and Social Research, the King Gustaf V's 80-Year Foundation, the Swedish
Rheumatism Foundation, the Stockholm County Council, the AFA insurance company
and the Agency for Science Technology and Research, Singapore.
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/.
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. For more information about
NCRR visit http://www.ncrr.nih.gov/.
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 http://www.nih.gov/.
Reference: Plenge RM et al.
TRAF1-C5 as a risk locus for rheumatoid arthritis -- a genomewide study.
NEJM 2007;357:1199 -1209.
Source: Trish Reynolds
NIH/National Institute of
Arthritis and Musculoskeletal and Skin Diseases
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