Gene links to spine disease

New hope has been offered for sufferers of spine disease following the discovery of two genes that increase the risk of a particular spinal condition, reported The Daily Telegraph. This breakthrough “could help tens of thousands of people in Britain who are victims of the condition ankylosing spondylitis, which causes inflammation in the joints between the vertebrae and can lead to bone erosion and the fusion of the bones in the spine,” the newspaper said.

The Independent reported that these genes have already been linked to the bowel condition, Crohn’s disease and that a “treatment for Crohn's disease that inhibits the activity of this gene is already in development. If it is shown to be safe and effective it is also likely to help those with ankylosing spondylitis”.

The stories are based on the findings of a large genome-wide association study. However, it is not actually yet certain if the findings will have an implication for treatment.

Where did the story come from?

This study was conducted by members of the Wellcome Trust Case Control Consortium and the Australo-Anglo-American Spondylitis Consortium and was supported by the Wellcome Trust. It was published in the peer-reviewed medical journal Nature Genetics .

What kind of scientific study was this?

This was a genome-wide association study which looked at the DNA sequence of a large number of individuals with specific diseases, including ankylosing spondylitis, multiple sclerosis, breast cancer, and autoimmune thyroid disease.

There were several different elements to the study. The researchers used complex methods to see how common particular variations within the DNA were in people with one of these diseases. They then compared the variations they found, first with 1,500 healthy British individuals (the control group) and then with the healthy individuals plus those in the other three disease groups. This second analysis provided a bigger group of “controls” to compare the cases with. To confirm the findings of this part of the study, the researchers then compared the variations they found with a new group of 471 people from North America who had ankylosing spondylitis and a new group of 625 healthy North Americans.

As a further part to the study, the researchers looked at a particular variation in a gene called IL23R which has been linked to ankylosing spondylitis in other studies (though it didn’t appear to be in this one). They reanalysed their data (comparing the cases to the combined group of controls) to see whether there was an association between the variation in this gene and the disease.

What were the results of the study?

Across all of their analyses, the researchers found many gene variations that were associated with these diseases. In particular, the newspapers noticed the finding that variations in two genes (ARTS1 and IL23R ) had strong links with ankylosing spondylitis, that is, they were more common in people who had this disease compared with those who were healthy or had another disease.

What interpretations did the researchers draw from these results?

The researchers concluded that their findings show that variations in these two genes increase the risk of ankylosing spondylitis. They discuss the evidence that variations in one of these genes have already been linked to Crohn’s disease and psoriasis, and that this may partly explain the reason why these diseases often occur together. They say that treatments that target this gene may prove effective for ankylosing spondylitis; however, they call for more research to understand the “mechanism which underlies the observed association”.

What does the NHS Knowledge Service make of this study?

This study reports reliable scientific research and raises some issues that will be of interest to the genetic research community:

• The causes of the diseases being investigated are complex. Ankylosing spondylitis is one of a group of related conditions known as the spondyloarthropathies, which are characterised by inflammation involving the joints, tendons and ligaments of, in particular, the lower back, but also other joints such as fingers and toes. These diseases also commonly cause problems other than joint involvement, such as eye conditions or skin rashes. Arthritis associated with psoriasis and with inflammatory bowel disease (such as Crohn’s disease and ulcerative colitis) is included in this group. For a long time, the spondyloarthropathies have all been known to have strong links to the gene HLA-B27 . Therefore, it is not surprising that there may be other possible genetic links between these diseases, as this study suggests. However, there are likely to be many other genetic and non-genetic links that remain to be identified. As the researchers themselves highlight, they may have missed further real associations between other variants and the diseases.
• The variations on the two genes of interest here – ARTS1 and IL23R – are not unique to people with ankylosing spondylitis and also occur in large numbers of healthy people. Having the variation does not mean you will have the disease.
• It is also important to note that readers of the newspapers should not misinterpret the headlines of “arthritis treatment hope” or “hope for spine disease sufferers” and confuse the disease that this research relates to with the much more common conditions of mechanical lower back pain or osteoarthritis.

It isn’t possible to say whether there will be any implications for the treatment of ankylosing spondylitis from these findings. However, the link between IL23R and the disease is an exciting one considering that the research into treatments for Crohn’s disease, which targets this gene, is quite far advanced.

Sir Muir Gray adds...

This type of targeted genetic research helps us define different types of disease and develop specific treatments.