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Genetic study sheds light on auto-immune arthritis which may have relevance for coeliac disease

Ankylosing Spondylitis (AS) is a common auto-immune arthritis which causes pain and stiffness of the spine, and in serious cases, progressive fusion of the vertebrae and other affected joints. A team of researchers from the universities of Bristol and Oxford (UK), Toronto (Canada), Queensland (Australia) and Texas (US) have used a technique called genome-wide association to get a better understanding of how an individual’s genetic make up may predispose them to AS.

The technique used by researchers measured millions of genetic markers both in people with the disease and people without, theorising that markers that are more frequent in individuals with the disease are more likely to be involved in the condition. They found an additional seven genes likely to be found in the condition, bringing the total number known to be involved in AS to thirteen.

Some of the new genes are known to be involved in inflammatory and immune processes, which would give further clues as to how the disease arises. Two of the new genes are also indicated in other auto-immune diseases such as Crohn’s disease and coeliac disease.

Researchers were also able to demonstrate an interaction between a genetic mutation called HLA-B27 and mutation in a gene called ERAP1. The ERAP1 mutation only predisposed those who tested positive for the HLA-B27 mutation to the disease.

Dr David Evans explained that this is an important finding because it is one of the first convincing examples of a genetic mutation influencing another mutation in the development of a disease. This implies there may be examples of this phenomenon in other common diseases that are as yet unknown.

The study also narrows the previously wide field of theories as to how AS is caused, by very strongly suggesting which of the competing hypotheses may be correct. The study has also identified a single genetic marker that could be used to diagnose AS, which is currently difficult and expensive to diagnose in its early stages.

Source: Nature Genetics


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