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Unlocking the genetics and biology of ankylosing spondylitis
Date:7/10/2011

rlying the condition, the findings also strengthen evidence that a particular process by which signals are transmitted within cells known as the IL-23R pathway is involved in the disorder and could be a target for drugs.

The study also provided clues as to why a particular genetic variant known as HLA-B27 is associated with the disease. Scientists have known for almost forty years that this variant significantly increases the risk of developing the disease. Nine out of ten people with ankylosing spondylitis carry the variant. Whilst not everyone with the variant develops the condition, those who carry the variant are up to eighty times more likely to develop it than non-carriers. Yet despite this knowledge, the mechanism by which the variant causes the disease is still unknown.

The researchers found that variants of the gene ERAP1 interact with HLA-B27 to affect disease susceptibility one of the first confirmed examples of gene-gene interaction seen in humans. For individuals who carry HLA-B27, their risk of developing ankylosing spondylitis decreases by a factor of four if they also carry two copies of the protective variants of ERAP1.

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 found that some variants of ERAP1 protect against the development of ankylosing spondylitis by reducing the amount of peptide available to HLA-B27 within cells. The researchers believe that inhibiting ERAP1 may help treat the condition.

The researchers also analysed the genetic make-up of individuals with ankylosing spondylitis who did not carry the HLA-B27 variant and found associations with several ge
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Contact: Craig Brierley
c.brierley@wellcome.ac.uk
44-207-611-7329
Wellcome Trust
Source:Eurekalert

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