After a half-dozen pint-sized robots organize genetic material onto plates
and feed it into computers, Peter K. Gregersen, MD, painstakingly mines the
data, hoping to discover the unique genes that make some people more
susceptible to rheumatoid arthritis (RA).
Gregersen, head of the Feinstein Institute’s Robert S. Boas Center for
Genomics and Human Genetics in Manhasset, N.Y., and his team are edging closer
to solving the puzzle. They recently announced the discovery of two new genes
that indicate a higher risk of developing RA, increasing the number of specific
genes now definitively linked to the disease. By the time Gregersen and his
colleagues finish their mission, probably 10 to 20 risk genes -- or more --
will be identified.
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“I think that will happen sooner than we think,” Gregersen says. “I would
guess within five years we will have all of the common and rare genetic
variants involved in RA mapped out.”
Why Map Rheumatoid Arthritis Genes?
When this happens, “it’s going to have a very large impact because we will
have a better sense about what is going wrong in the bodies of people with RA,”
This is welcome news for the 2.1 million people with RA and those at risk
for developing it. An autoimmune disease, RA occurs when the immune system
attacks the joints, causing inflammation and chronic pain, loss of function,
and eventual disability if left untreated. Understanding the genetic roots of
RA will enable doctors to identify people most likely to get the disease -- and
even treat them -- before they have joint pain and other symptoms.
And that’s not all. Doctors may one day be able to analyze a person’s genes
to figure out which RA drug will work best, eliminating trial and error.
Identifying RA’s genes may also lead to newer and more effective targeted
Genetic Clues to Rheumatoid Arthritis
Doctors already have identified several risk factors for RA, including:
gender (women are two to three times more likely than men to develop RA);
mature age (RA typically strikes people between the ages of 30 and 55); family
history; and smoking.
The gene project started about 10 years ago when the North American
Rheumatoid Arthritis Consortium (NARAC) was formed. Researchers knew only that
genetic factors likely played a role in predisposing people to RA, but they
knew little about the specific genes involved.
With the help of robots and other new tools such as microarray analysis,
which allows researchers to swiftly sort through genetic material, Gregersen
reported last fall that a variant of the gene called STAT4 can boost a person’s
risk for RA or lupus (another autoimmune disease) by 30% to 60%, depending on
how many copies of the gene a person has.