News article from UT site:
http://publicaffairs.uth.tmc.edu/Media/newsreleases/nr2007/DisablingArthritis.htm
UT Rheumatologists Discover Two 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 Australia’s 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. "We’ve 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 we’ve 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 weren’t many options. I was told to take anti-inflammatories and stay as active as possible. It’s fascinating to see how far we’ve 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 TASC’s administrative core.
Media Contact
Meredith Raine
Meredith.Raine@uth.tmc.edu
Media Hotline: 713-500-3030
Here's another news story that was just published:
http://www.huliq.com/38928/major-genetic-breakthrough-for-ankylosing-spondylitis-brings-treatment-hope
Major genetic breakthrough for ankylosing spondylitis brings treatment hope
as well as some other Similar Stories
Rheumatologists Discover Two Genes Related to Disabling Form of Arthritis
Study reveals 2 genes linked to disabling arthritis
Researchers have developed model that mimics actual joints
Knee Buckling Can Be Downfall for Older Adults
Medication 'may have killed' arthritis patient
Research funded by the Wellcome Trust and the Arthritis Research Campaign has identified two genes implicated in the disease ankylosing spondylitis, a common disease primarily causing back pain and progressive stiffness. The research, published online today in Nature Genetics, suggests that a treatment currently being trialled for Crohn's disease may also be applied to this disease.
Ankylosing spondylitis affects as many as 1 in 200 men and 1 in 500 women in the UK, typically striking people in their late teens and twenties. Whilst it mainly affects the spine, it can also affect other joints, tendons and ligaments. More rarely, it can affect other areas, such as the eyes, lungs, bowel and heart.† High-profile sufferers of the condition include former England cricket captain Mike Atherton.Now, using a technique known as genome-wide association scanning, researchers led by Professors Lon Cardon, Matthew Brown and Paul Wordsworth, from the Wellcome Trust Centre for Human Genetics at the University of Oxford have analysed DNA samples from 1,000 patients with ankylosing spondylitis and a further 1,500 people unaffected by the disease in search of genetic mutations which, if present, increase a person's risk of developing the disease. The findings from this study were then confirmed by a team at University of Texas (Houston) led by Professor John Reveille.
"Ankylosing spondylitis is a painful and often very disabling disease," says Professor Brown. "Yet, our understanding of the causes of the disease, and hence our ability to treat it effectively, is relatively poor."
The researchers have identified two genes, ARTS1 and IL23R, which increase the risk of developing the disease. Together with the genetic variant HLA-B27, this takes the number of genes definitely known to be involved in the disease to three. A person carrying all three variants would be expected to have a one in four chance of developing the disease.
The IL23R gene plays a role in the immune response to infection, providing instructions for making a receptor present on the surface of several types of immune system cells. The receptor is involved in triggering certain chemical signals inside the cell that promote inflammation and help coordinate the immune system's response to infection. It is already recognised as playing a role in a number of autoimmune diseases, such as Crohn's disease (a type of inflammatory bowel disease) and psoriasis (a skin disease). Ankylosing spondylitis, Crohn’s disease and psoriasis are known to often occur together, and this genetic finding goes a long way to explain why.
Professor Brown believes that the unexpected involvement of IL23R in ankylosing spondylitis provides a major step towards being able to treat the disease. "We already know that IL23R is involved in inflammation, but no one had ever thought it was involved in ankylosing spondylitis," says Professor Brown. "A treatment for Crohn's disease that inhibits the activity of this gene is already undergoing human trials. This looks very promising as a potential treatment for ankylosing spondylitis."
Scientists have known that there is a genetic component to ankylosing spondylitis for 37 years, since the discovery of the gene HLA-B27. However, how this gene led to disease is not known. Professor Brown believes that the gene ARTS1 may hold the answer.
A protein created by the HLA-B27 gene takes fragments of pathogens and displays them on the outside of immune cells. These fragments then trigger the immune system to fight against the pathogen. ARTS1 is involved in breaking up the pathogen into "bite-size chunks" that can be displayed by HLA-B27.
"This strongly suggests that in ankylosing spondylitis, there are problems with the information that the HLA-B27 protein receives, thereby causing the disease," says Professor Brown.
Scientists believe that ankylosing spondylitis may be triggered in genetically-susceptible people by bacteria commonly found in the gut. Why this should be the case is unclear, but it is hoped that the new genetic discoveries will help answer this question.
"These findings are very exciting and show the value of exploring the genetics of disease," says Dr Mark Walport, Director of the Wellcome Trust. "It usually takes many years between genetic discoveries and new treatments for disease. In this case the two genes discovered to be associated with ankylosing spondylitis provide striking insights into the mechanisms of the disease and offer a possible new pathway for treatment."
The study is a collaboration between the Wellcome Trust Case Control Consortium and the Australo-Anglo-American Spondylitis Consortium funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases.
"These genetic studies involve large patient samples and require expertise over a wide range of scientific specialities", says Professor Cardon. "Bringing together these two consortia was the final key that enabled these exciting discoveries."-Wellcome Trust
|