The new study finds that certain pairs of variants in the ERAP1 gene are found only in people with the inflammatory rheumatic disease ankylosing spondylitis.
In the Proceedings of the National Academy of Sciences, researchers from the University of Southampton in the UK describe how they found the enzyme ERAP1 is highly variable in humans, and specific combinations of variants are found in people with ankylosing spondylitis.
Better understanding of these variations could lead to a genetic test that helps people become aware of the risk of ankylosing spondylitis earlier and improve disease prognosis, say the researchers.
Ankylosing spondylitis is a chronic inflammatory disease that mainly affects joints in the spine. In severe cases, it can lead to complete fusion and rigidity of the spine, a condition that is sometimes called "bamboo spine."
In most cases, ankylosing spondylitis first develops in young adults aged 20-30, and the disease is around three times more common in men than in women.
Estimates suggest up to 0.5% of people in the US have the condition, while in the UK, where the study was conducted, around 200,000 people have been diagnosed with it.
There is no cure for ankylosing spondylitis, although treatment can reduce symptoms and pain. Also, the earlier it is diagnosed, the greater the chance of slowing progression.
A genetic test could 'revolutionize the management of ankylosing spondylitis'
The researchers say as it can take up to 10 years to diagnose the disease, a genetic test could revolutionize the management of ankylosing spondylitis.
Tim Elliott, co-leader of the study and professor of Experimental Medicine at Southampton, says:
"These natural variations in ERAP1, which are normally involved in T-cell immunity, predispose individuals to ankylosing spondylitis. We have also discovered how variations in ERAP1 change its enzyme function - and this means that it might actually be a target for developing new drugs to treat ankylosing spondylitis."
ERAP1 stands for endoplasmic reticulum aminopeptidase 1. One of its functions is to cut proteins into smaller pieces called peptides that can be recognized by the immune system. If the immune system decides they are foreign, it responds by triggering the infected cell's self-destruct mechanism.
Several variations in the ERAP1 gene have been found to influence the risk of ankylosing spondylitis, although little is known about their effect and exactly how they might lead to the disease. Other genetic and environmental factors - many of which are unknown - are also thought to influence the chance of developing the condition.
Certain pairs of ERAP1 variations linked to ankylosing spondylitis
For their study, Prof. Elliott and colleagues sequenced the DNA code of ERAP1 variations found in patients with ankylosing spondylitis and people without the disease.
Each person carries two copies of the ERAP1 gene that codes for the enzyme. The study picked up at least 13 variants of ERAP1 and found certain pairs were present in patients with ankylosing spondylitis that were not in the disease-free controls.
The team did not set out to look specifically at ERAP1 variants in ankylosing spondylitis - they were studying links to cancer when they made these discoveries. They are continuing to study ERAP1 variations for any links with head and neck cancer.
In October 2014, Medical News Today learned of a study that suggests, contrary to what many scientists believe, Egyptian pharaohs were unlikely to have suffered from ankylosing spondylitis.Using CT scans, researchers showed that it was more likely that they suffered from the degenerative spinal condition known as diffuse idiopathic skeletal hyperostosis (DISH).