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Researchers identify new Risk Factor Gene
for Rheumatoid Arthritis
MANHASSET, NY -- Scientists at The Feinstein
Institute for Medical Research and a team of
collaborators from across the country have
identified a new risk factor gene for
rheumatoid arthritis.
The paper will be published in Nature
Genetics and the finding brings light to the
nature of the disease.
The gene, dubbed REL, is a member of the NF-κB
family, important transcription factors that
have many roles in the body. The NF-κB
family seems to have a big hand in
regulating the body’s immune response as
well.
is a key switching point for many
“The NF-κB cellular activities,” said Peter
K. Gregersen, MD, head of the Robert S. Boas
Center for Genomics and Human Genetics at
the Feinstein Institute and lead author of
the study.
Dr. Gregersen is part of a nationwide
consortium of investigators seeking to
identify risk genes for rheumatoid arthritis
(RA).
The hope is to figure out the genetic
triggers and identify treatments that block
this autoimmune process.
In theory, such advances can point the way
to understanding other autoimmune disorders.
About one percent of the population will
develop rheumatoid arthritis, which can be
crippling.
REL pathway.
is a key regulator of CD40, which works
through the NF-κB
“This paper represents the latest in a
series of important publications chronicling
an exceptionally productive collaboration
between extramural and intramural scientists
through the North American Rheumatoid
Arthritis Consortium,” said Daniel Kastner,
MD, PhD, clinical director of the National
Institute of Arthritis and Musculoskeletal
and Skin Diseases.
“In describing yet another gene in the CD40
signaling pathway that is involved in
rheumatoid arthritis susceptibility, this
paper reinforces the possibility of
targeting this pathway in selected patients
with this debilitating illness.”
The consortium has helped identify many
genes involved in rheumatoid arthritis but
this genetic finding is significant because
of its key role in immune system regulation.
It did not reveal itself in previous genetic
studies because the sample size was just not
large enough.
In previous studies, genetic samples from
about 2,000 patients were used to identify
markers associated with risk for RA. In the
latest study, the scientists analyzed
samples from 4,000 RA patients and controls.
According to Dr. Gregersen, this particular
genetic variant is rather common, found in
about a third of people in North America.
That means that it must confer an important
survival advantage.
That said, scientists need to figure out its
role in increasing the risk for RA. Next on
the research agenda is to see if they can
measure how the gene is regulated under
specific conditions that set the stage for
RA.
“There are a huge number of unknowns,” said
Dr. Gregersen. “These findings are clear –
this pathway is involved – but there is a
lot of work to be done.”
Genetic differences between individuals help
scientists understand many diseases. But
this is just the beginning, added Dr.
Gregersen.
Today,
most markers that are used to identify genes
represent variants that occur in more than
five percent of the population.
The next wave in genetic screening will have
to include the variants that occur in less
than one percent of the population.
In addition to the Feinstein Institute, part
of the North Shore-LIJ Health System, other
centers that are part of the RA consortium
include: the University of Texas, MD
Anderson Cancer Center; the Genetics and
Genomics Branch of the National Institute of
Arthritis, Musculoskeletal and Skin
Diseases; the Rowe Program in Genetics,
University of California at Davis; the
Russell Medical Research Center for
Arthritis, Department of Medicine,
University of California, San Francisco;
Brigham and Women's Hospital at Harvard
Medical School; University of Colorado
Denver School of Medicine; University of
Nebraska Medical Center; Central Hospital in
Finland; University of Pittsburgh Medical
Center; University of Alabama at Birmingham;
Mount Sinai Hospital; University Health
Network in Ontario, Canada; and Celera.
The work was supported by grants from the US
National Institutes of Health NO1-AR-2-2263
(P.K.G.), RO1 AR44422 (P.K.G.) and by the
Eileen Ludwig Greenland Center for
Rheumatoid Arthritis and the Muriel Fusfeld
Foundation. The work was also supported in
part by the Intramural Research Program of
the National Institute of Arthritis and
Musculoskeletal and Skin Diseases and by
grants from the Canadian Institutes for
Health Research (MOP79321) and Ontario
Research Fund (RE01061) and a Canada
Research Chair to K.A.S.
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