UQDI researchers lead the way in a US$4m project to unravel the genetics of a debilitating form of arthritis

3 Oct 2012

Ankylosing spondylitisResearchers at The University of Queensland Diamantina Institute (UQDI) and their international collaborators will continue unravelling the mechanisms underlying a particular type of early-onset arthritis, thanks to a multi-million dollar grant.

The American National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) confirmed a US$4m grant for researchers to identify further genetics associated with ankylosing spondylitis.

Ankylosing spondylitis (AS) is a debilitating form of arthritis, affecting up to 100,000 Australians. The disease mainly affects the joints of the spine and the pelvis, causing pain and joint stiffness. AS causes bone material to be laid down in the affected joints, eventually rendering them immovable.

“Over the first five years of this program, our genetic discoveries have identified over 40 new genetic variants involved in AS.  These findings have revolutionised research in the disease, and have already led to new treatments for the condition,” says Professor Matt Brown, Director of The University of Queensland Diamantina Institute.

Symptoms of AS can manifest as early as during adolescence, and current treatments consists of immune suppression along with pain management and reduction of the inflammation. Whilst these treatments are highly effective at reducing joint pain, as yet there is no treatment which has been show to stop the progressive joint fusion, or induce remission in AS.

Genetics play a crucial role in AS, with the first marker gene for the disease, HLA-B27, discovered as early as the 1970s. However, since only approximately 5% of people with the HLA-B27 gene develop AS, other genetic factors also had to be involved.

“So far we have only looked at common genetic variants which make up <1% of the genetic variation between individuals.  Over the next five years, using new DNA sequencing technology, we will be able to look at the rest of the genetic variants,” Professor Brown commented.

“This should yield another rich harvest of discoveries about the root causes of this condition.” 

In 2006, researchers from Australia, the UK, Canada and the US formed The Australo-Anglo-American Spondyloarthritis Consortium (or Triple ‘A’ Spondyloarthritis Consortium - TASC) to investigate various aspects of AS. The Australian arm of TASC, led by Professor Matt Brown, concentrated on the genetics of AS.

The group used a revolutionary technique called Genome Wide Association Scanning (GWAS) to detect differences in the genetic makeup of AS patients and healthy subjects. Over the following years, TASC researchers identified more than 40 genetic variants associated with the disease, explaining about a quarter of the risk of developing the condition.

While these discoveries led to a better understanding of AS and have already contributed to new therapeutic approaches, they still do not reveal the entire picture of AS. Building on the results obtained to date, TASC researchers will now use a different set of techniques to identify even more AS associated genes, but also to deepen their knowledge of previously identified associations.

In this follow-up project, financed by a US$4M grant from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (an institute of the US National Institutes of Health), Professor Matt Brown and his team of researchers at UQDI will again concentrate on the deeper genetics of AS.  

 “We are delighted through this funding to be able to continue to work with our close North American and British collaborators in working to solve the causes of this common, under-researched disease,” says Professor Brown.