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UT rheumatologists discover 2 genes related to disabling form of arthritis

HOUSTON (Oct. 22, 2007)Work done in part by researchers at The University of Texas Medical School at Houston has led to the discovery of two genes that cause ankylosing spondylitis, an inflammatory and potentially disabling disease. The findings are published in the Oct. 21 online edition of Nature Genetics, a journal that emphasizes research on the genetic basis for common and complex diseases.

John D. Reveille, M.D., professor and director of the Division of Rheumatology and Clinical Immunogenetics, in conjunction with Matthew A. Brown, M.D., professor of immunogenetics at Australias University of Queensland, led research done by the Triple A Spondylitis Consortium Genetic Study (i.e. the TASC or Australo-Anglo-American Spondylitis Consortium).

The international team of researchers worked with investigators from the British Wellcome Trust Case Control Consortium, and together they made the genetic discovery.

Reveille, chief of rheumatology at Memorial Hermann Texas Medical Center, said the discovery of genes ARTS1 and IL23R brings the scientific community two steps closer to fully understanding ankylosing spondylitis or AS, a chronic form of arthritis that attacks the spine and also can target other joints and organs in the body.

Weve long known that the HLA-B27 gene accounts for 40 percent of the overall cause of AS, said Reveille, the principal investigator of TASC. Now we have found two new genes. Together with HLA-B27, these genes account for roughly 70 percent of the overall cause. That means weve almost nailed this disease. Within the next year, I predict we will have identified all the genes that play a role in this insidious disease. There is more exciting news to come.

The recent discovery is based on work from the largest and most comprehensive genome-wide association scan conducted to date. In this part of the research project, investigators were searching for genetic information related to AS, as well as autoimmune thyroid disease/Graves Disease, breast cancer and multiple sclerosis. Reveille, the George S. Bruce, Jr. Professor in Arthritis and Other Rheumatic Diseases, said the most significant findings were in AS, a disease that generally strikes patients in their teens, 20s or 30s.

ARTS1 and IL23R show a new pathway of causation, Reveille said, and this could lead to new therapies for the arthritic condition, which can cause a complete fusion of the spine, leaving patients unable to straighten and bend.

The identification of the two new genes also could help physicians identify patients who are at the highest risk for developing AS.

For example, if you have a family member with AS, a simple blood test would be able to tell us if you are also at risk, Reveille said. We could offer screenings for people with back pain. In the past, the HLA-B27 test was all we had. Now we potentially have more tests.

Steve Haskew, who has lived with AS for thirty years, said the genetic discovery offers hope to patients especially those who are newly diagnosed.

When I first started experiencing problems lower back pain, the aching joints no one could tell me what was wrong, said Haskew, 59, co-leader of an AS support group that meets every other month at the UT Medical School at Houston. It took 10 years before a rheumatologist diagnosed me with AS. Back then, there werent many options. I was told to take anti-inflammatories and stay as active as possible. Its fascinating to see how far weve come and how much has been learned about the disease since then.

The research done by Reveille and his colleague Xiaodong Zhou, M.D., associate professor of medicine in Division of Rheumatology and Clinical Immunogenetics, was supported in part by the Center for Clinical and Translational Sciences (CCTS) at The University of Texas Health Science Center at Houston.

This is a success story for genetics work, and I think it will lead the way for other work to be done, Reveille said.

The Spondylitis Association of America (SAA) oversaw the nationwide recruitment of patients and families for the study.

This is the most significant breakthrough in AS genetic research since HLA-B27 was uncovered 34 years ago, and SAA played a significant role in making the study possible, said SAA Associate Executive Director Laurie Savage, who is co-principal investigator for TASCs administrative core.


Contact: Meredith Raine
University of Texas Health Science Center at Houston

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