by Chris Miller | Posted on 8/29/2012
It is known that ankylosing spondylitis (AS) and related diseases, also known as a group of diseases called "spondyloarthritis (SpA)", have a strong genetic component. Thus, those with a certain genetic makeup are more prone to getting SpA. One theory is that an environmental trigger will cause those with certain genes to develop AS. This trigger, however, has not been found, although there are theories that microbes such as gut bacteria could be involved in the pathogenesis of the disease.
It should be clarified that ankylosing spondylitis is not an infectious disease like the flu, nor are other forms of spondyloarthritis. One cannot shake hands with someone with ankylosing spondylitis and simply contract it.
The HLA-B27 antigen, discovered almost forty years ago, is thought to account for 20 to 50% of the total genetic risk for this disease. Along those lines, if a family member has spondyloarthritis and you test positive for HLA-B27, your chance of getting the disease increases to 20%, if you are under age 40. If you are over 40, your chance of developing spondylitis is very low. If you have AS, the likelihood of passing it on to your children is relatively low. There is approximately a 50% chance that the child of one HLA-B27 positive parent will inherit the gene, but only a small percentage of those will develop AS.
In the past five years, a number of new genes besides HLA-B27 have been discovered that appear to contribute to ankylosing spondylitis susceptibility.
ERAP1 (formerly called ARTS1) is one of the newest genes related to AS to be found. It was discovered in 2007 by the Triple-A (Australo-Anglo-American) Spondyloarthritis Consortium genetic study, also known as TASC. This study is an ongoing collaborative effort by an international team of researchers in the U.K., Australia and the U.S.
In July, 2011, the U.K. branch of the TASC study sent a press release stating that ERAP1 appears to interact with HLA-B27 to increase AS disease susceptibility and that this is "one of the first confirmed examples of gene-gene interaction seen in humans.
"ERAP1 plays a role in breaking down proteins within the body into smaller molecules known as peptides. The gene interacts with HLA-B27 to affect how these peptides are presented to the immune system. This is an essential process for mounting an immune response to invading pathogens, but when it goes awry it can result in the immune system causing inflammation and damaging tissue...The researchers believe that inhibiting ERAP1 may help treat the condition."
Now, a new study published online on August 15, 2012 in the Annals of Rheumatic Diseases helps confirm that there is an "association between several polymorphisms located in ERAP1 and SpA as a whole." Thus, ERAP1 appears to not only be related to AS, but all of the spondyloarthritis conditions.
It is hoped that by discovering new genes and examining how they interact, new medication targets may be found, possible new diagnostic testing could be developed and that the genes may help point a way to the trigger of spondyloarthritis.
Further Reading & References
About the writer: Chris Miller is the Director of Programs at the Spondylitis Association of America and is Managing Editor of SAA's news magazine, Spondylitis Plus. He has been at SAA for nine years.
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