Linking of insulin signaling, the tricarboxylic acid cycle and epigenomic reprogramming cellular pathways with candidate gout-associated genes. Credit: Nature Genetics (2024). DOI: 10.1038/s41588-024-01921-5

A major international study has found that gout is a chronic illness in which genetics is a major cause, rather than the lifestyle choices of the sufferer.

Led by University of Otago researchers, the genome-wide association study, published in Nature Genetics, analyzed the genetic information of 2.6 million people.

Researchers analyzed amalgamated DNA data sets from around the world. About three quarters of the data was from customers of 23andMe, Inc., a direct-to-consumer genetics and preventative health company, who consented to participate in research.

The researchers found inherited genetics is an important part of why some people get gout and most others don’t.

Senior author Professor Tony Merriman, of Otago’s Department of Microbiology and Immunology, hopes the findings will remove some of the stigma around gout.

“Gout is a chronic disease with a genetic basis and is not the fault of the sufferer—the myth that gout is caused by lifestyle or diet needs to be busted.

“This widespread myth causes shame in people with gout, making some people more likely to suffer in silence and not go and see the doctor to get a preventive drug that lowers urate in the blood and will prevent their pain.

“People need to understand that while specific dietary factors, such as eating red meat, can trigger gout attacks, the fundamental cause is high urate levels, crystals in the joints, and an immune system primed to ‘attack’ the crystals—genetics plays an important role in all of these processes.”

The research identified a large number of immune genes and immune pathways that provide new targets and approaches for preventing gout attacks.

Professor Merriman hopes these findings will lead to improved treatment for gout sufferers.

“We hope that, in time, better and more accessible treatments will become available with the new targets we identified,” he says.

One such option could be the repurposing of a drug used to treat a range of other immune-related diseases, including rheumatoid arthritis—tocilizumab targets a receptor for an immune signaler, interleukin-6, which the research identified as a new gene for gout.

Information about gout:

• Gout is the most common form of arthritis in men; it affects about 3–4 times more men than women.
• Gout attacks are caused by severe inflammation in the joints that arises from reaction to crystals of urate. These crystals form in the joints when urate levels in the body are high.
• Diet plays a very small role in high urate levels but it is well established as a trigger of gout in people with urate crystals in their joints.
• Gout can be effectively treated by drugs (such as allopurinol) which lower the urate in the blood and prevent urate crystal forming in the joints (or dissolve them if they are already there).
• Gout is a chronic disease, so treatment is lifelong.