Two New Arthritis Genes Identified

Main Category: Arthritis / Rheumatology
Also Included In: Genetics
Article Date: 22 Oct 2007 - 14:00 PDT

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In a world first, a UQ scientist has discovered two new genes responsible for one-third of the risk of developing a hereditary and debilitating form of arthritis known as ankylosing spondylitis.

The discovery, headed by Professor Matthew Brown, from UQ's Diamantina Institute for Cancer, Immunology and Metabolic Medicine, is the most significant discovery in this disease since the first gene behind spondylitis was identified 37 years ago.

The study was performed by both the Wellcome Trust Case Control Consortium (WTCCC) and the Australo-Anglo-American Spondylitis Consortium (known as TASC), accessing a grant pool of $16.6 million (£7 million) and $7 million (US$5.5 million) respectively.

Professor Brown's work was assisted by Professor John Reveille from the Division of Rheumatology and Clinical Immunogenetics at the University of Texas, and involved a team of researchers in Australia, England and North America.

"The identification of the two new genes will assist doctors to identify those people at high risk of developing ankylosing spondylitis," Professor Brown said. "They also point to basic processes which cause this disease, for which there is no current treatment to prevent its progression.

"Together with the main gene, HLA-B27, the discovery of the two new genes, dubbed ARTS1 and IL23R, means we can now account for 70 percent of the overall cause of ankylosing spondylitis.

"At this rate, we should have identified all of the genes that play a role in this damaging condition within the next 12 months."

Published in the latest edition of prestigious international journal, Nature Genetics, Professor Brown's discovery is expected to rapidly lead to new therapeutics to treat ankylosing spondylitis, with clinical trials expected to occur over the next couple of years.

Ankylosing spondylitis is the second-most common form of arthritis and affects around one in 200, mainly young, adults, with 22,000 Australians currently managing the condition.

It causes back pain and progressive stiffness of the spine, and can also damage other joints, the eyes and heart. In its most severe form, it leads to a complete fusion of the spine leaving patients unable to straighten and bend.

The genetic findings also largely explain why three conditions - psoriasis (skin inflammation and excessive skin production), Crohn's disease (inflammatory bowel disease), and ankylosing spondylitis - commonly occur together, something which had never previously been understood.

The results are among the first in a roll-out of life-changing discoveries from the world's largest genetic study involving WTCCC and TASC scientists on three continents.

To make his discovery, Professor Brown scanned 14,500 genetic variants affecting proteins known as nonsynonymous SNPs (nsSNPs) from 2500 people.

The main equipment used at UQ Diamantina was a micro array genotyper, capable of simultaneously analysing millions of possible genetic sequences.

The University of Queensland, Brisbane Australia