Two new genes found for rheumatoid arthritis

By Gene Emery

BOSTON (Reuters) - Two genetic mutations raise the risk of rheumatoid arthritis, one by as much as 87 percent, researchers reported on Wednesday in a discovery that sheds more light on a complex and baffling disease.

They said their findings also show a link between rheumatoid arthritis and other diseases caused when the immune system mistakenly attack healthy tissue, such as lupus.

People who had two copies of one gene, found in a region known as STAT4, had a 60 percent higher risk of rheumatoid arthritis, the international team of researchers reported in New England Journal of Medicine.

A double shot of the second genetic mutation, in an area known as TRAF1-C5, increased the risk by 87 percent, the same team of researchers reported in a second study, based on a scan of more than 3,000 people.

The findings do not apply to osteoarthritis, which affects 21 million Americans and is known as "wear and tear" arthritis because it breaks down the cartilage that cushions the ends of bones. Rheumatoid arthritis is an inflammatory condition that affects 2.1 million people in the United States.

"There are now five genes that we are quite certain are involved in rheumatoid arthritis. Five at a minimum," said Peter Gregersen of the Feinstein Institute for Medical Research in Manhasset, New York.

"I suspect there's another three to five at least to be found. The story in rheumatoid arthritis is going to be very similar to type-1 diabetes, which is now is generating on the order of 10 to 20 definite risk genes. I would not be surprised if we ended up somewhere in that realm."

Treatments for rheumatoid arthritis include dangerous immune-suppressing drugs, which can leave patients vulnerable to infections and cancer. Researchers hope that if they can understand the genes involved in the disease, they can design better treatments.

SCANNING FOR DISEASE GENES

The new reports are only the latest in a series of studies stemming from new technology that enables researchers to pinpoint areas in the genetic code that are either responsible for various medical conditions or increase a person's risk for disease.

In the case of STAT4, the Gregersen team discovered an aberrant form of the gene in the genetic code of 27 percent of 4,000 Swedish and North American patients people with rheumatoid arthritis.

However, it was also found in 22 percent of cancer patients with no history of rheumatoid arthritis.

The researchers also discovered that having two copies of same gene, located on the second-largest chromosome, more than doubled the risk of developing systemic lupus erythematosus, suggesting a link between arthritis and the autoimmune disease that can affect the kidneys, heart, lungs and blood.

"From a practical point of view for using this information for diagnosis or making decisions about an individual, it's not very useful," said Gregersen. "But from the point of view of giving you insight into what pathways are actually involved in the pathogenesis of the disease, it's hugely important."

STAT4 controls a signaling molecule involved in the effects of immune system compounds called cytokines, including such as IL-12 and some types of interferon. They are involved in inflammation.