New study highlights role of common gene variations in ankylosing spondylitis

New research has revealed an insight into the genetic underpinnings of ankylosing spondylitis that could aid the future treatment of the disease.

Led by the University of Oxford and published in the Proceedings of the National Academy of Sciences, the study has indicated that the specific genetic variants associated with the onset of the condition may be more common than previously thought.

The true genetic origin of ankylosing spondylitis
For this study, data on 213 ankylosing spondylitis patients and 46 people with rheumatoid arthritis was analysed in order to examine the common scientific assumption that ankylosing spondylitis is mostly associated with unusual ERAP1 genotypes.

It is known that two genes involved in antigen processing and presentation to the immune system - HLA-B*27 and ERAP1 - have a big role to play in driving the disease, with previous studies indicating that rare ERAP1 variants that dramatically alter antigen processing functions are responsible.

However, this new research found that it was in fact common variants of ERAP1 that were responsible for regulating people's ankylosing spondylitis, rather than rare variations or unusual genetic combinations.

What this could mean
Ankylosing spondylitis is a chronic condition that can lead to back pain, stiffness, fatigue and impaired mobility that develops over time. The causes of the disease are not currently well understood, so further research into its genetic origins could make it easier for scientists to create new and more effective therapies.

The researchers said: "This has important potential implications for future studies addressing the development of ERAP1 inhibitors as new treatments, not only for ankylosing spondylitis but also in other diseases genetically associated with ERAP1."

Professor Paul Wordsworth, of Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, said: "More than 40 years after the first genetic association was described between ankylosing spondylitis and HLA-B27, a second strong genetic link was identified with another gene - ERAP1. Both these genes are involved in the process by which foreign proteins are recognised by the immune system and the association with ERAP1 is only found in people with AS who are themselves HLA-B27 positive.

"Variants of ERAP1 that reduce its function are associated with protection against AS raising the possibility that small molecule inhibitors of ERAP1 might be developed as drugs for the condition."

Arthritis Research UK's view
Dr Katherine Free, research engagement manager at Arthritis Research UK, said: "Ankylosing spondylitis is known to have a significant genetic link, and studies to date have identified over 40 genetic changes that are thought to contribute to an individual's risk of developing this disease.

"Previous research has shown that alterations within two particular genes, known as HLA-B*27 and ERAP1, have a particularly strong link to ankylosing spondylitis. This research sheds new light on the particular genetic changes within ERAP1 that are responsible for disease development. Identifying the effect that these genetic changes have on the immune system could pave the way for the development of new and more effective treatments for this condition."