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Tissue-Growth Gene Tied to Scleroderma
Date:9/19/2007

Finding is a step towards treating the autoimmune disorder

WEDNESDAY, Sept. 19 (HealthDay News) -- New research suggests a gene governing the growth of connective tissue is key to scleroderma, an autoimmune disease in which the body builds up thick layers of scar tissue in the skin and around internal organs.

The British finding is just "a piece in a jigsaw puzzle" explaining the genetics behind scleroderma, which is also known as systemic sclerosis, said co-author Gisela E. Lindahl, a principal research fellow at the Royal Free and University College Medical School in London.

But the study does implicate the connective-tissue growth factor (CTGF) gene in scleroderma, which affects some 30,000 Americans and is estimated by the Scleroderma Foundation to cause 10,000 deaths in the United States annually.

Her team published its findings in the Sept. 20 issue of the New England Journal of Medicine.

In the study, the London team compared the CTFG gene in 500 people with sclerosis and 500 without the condition. This was a relatively large study, involving about 10 percent of all people with sclerosis in Britain.

The researchers found one particular form of the gene to be present in 30 percent of those with scleroderma. It was even more common in patients with pulmonary fibrosis, in which the scar tissue is deposited in the lungs.

This form of the gene was also found in 20 percent of those without the condition, however. So, all that can be said is that the protein produced by the variant gene "is one of the substances pushing the disease to develop," she said.

"At the moment, we're not certain how this works," Lindahl said. "It stimulates the cells to do various things ongoing in fibrosis. It is important in cell proliferation, possibly in cell differentiation, the changing of a cell from one form to another. There are a few different properties of the protein, which may be why higher levels of it are associated with the disease."

"We don't want people to think we have found the final solution and answer," said Carol Feghali-Bostwick, an assistant professor of medicine and pathology at the University of Pittsburgh, and a member of the Scleroderma Foundation board of directors. "But they have shown that having this particular sequence in your DNA puts you at risk. It is a good candidate gene, but it doesn't explain why some people have the sequence but not the disease."

The researchers have found that the CTGF gene variant has lost the ability to regulate the production of the CTGF protein.

"They took an extra step in understanding the variant gene's functional role," Feghali-Bostwick said. "They have shown that this gene is not turned off as well as it should be."

The finding is consistent with reports of high levels of the CTGF gene in other diseases characterized by excessive scarring and fibrosis, including cirrhosis of the liver, some kidney diseases associated with diabetes and some heart conditions, the report said.

There is no immediate medical application of the finding, Lendahl said, "but all this knowledge will be useful in developing therapies to treat this disease. We know that this is one of the substances pushing the disease to develop, so if we develop ways to reduce CTGF, we may reduce the symptoms. We are trying to work out how proteins regulate this process so that we could develop drug therapies."

More information

There's more on scleroderma at the U.S. National Library of Medicine.



SOURCES: Gisela E. Lindhal, Ph.D., principal research fellow, University College Medical School, London; Carol Feghali-Bostwick, Ph.D., assistant professor, medicine and pathology, University of Pittsburgh; Sept. 20, 2007, New England Journal of Medicine


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