Scientists Search For Rheumatoid Arthritis Genes

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.

“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,” he says.

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 treatments.

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.