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Genes Boost Risk for Rheumatoid Arthritis, Lupus
Date:9/5/2007

uals with rheumatoid arthritis or lupus. Using gene mapping, the researchers identify STAT4 as a gene involved in increasing the risk for both diseases.

"Although we don't know how this gene variant changes immune function, it is clear that this finding places STAT4 pathways directly in a scheme of pathogenesis for both [rheumatoid arthritis] and lupus," Gregersen said. "This shows that a single gene can overlap autoimmune disorders."

Gregersen's group found that some 22 percent of people carry this particular form of STAT4, but that percentage rises to 27 percent in people with rheumatoid arthritis. This STAT4 variant increases the risk of developing rheumatoid arthritis by 32 percent. For people with two copies of this variant, the risk is increased by 60 percent, the researchers noted.

Patients with the STAT4 variant have about double the risk of developing lupus compared with people without the variant, the researchers reported.

In another study by Gregersen and colleagues, STAT4 was identified as an important risk gene in Koreans with rheumatoid arthritis. That paper appears in the September issue of Molecular Medicine.

Studies in mice with rheumatoid arthritis have shown that blocking STAT4 can prevent or relieve arthritis, suggesting that STAT4 could be a target for new therapies, Gregersen noted. In addition, STAT4 could help researchers identify triggers for rheumatoid arthritis, develop diagnostic tests, and to even predict who will best respond to treatments, he said.

Gregersen said his team is also looking at what role, if any, STAT4 might play in other autoimmune diseases.

In the other New England Journal of Medicine study, Gregersen's team looked at the genotype of 1,522 people with rheumatoid arthritis. They then compared these with the genotype of 1,850 people without the disease.

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