New study emphasizes the importance of genetics in gout research

BIRMINGHAM, Ala. – Tony Merriman, Ph.D.,  professor in the University of Alabama at Birmingham Division of Immunology and Rheumatology and internationally recognized leader in the genetic basis of gout, has published “A genome-wide association analysis reveals new pathogenic pathways in gout” in the journal Nature Genetics.

The study’s most significant outcome is identifying 148 previously unreported loci in urate and gout. This gives researchers promising targets to help address gout, a painful form of arthritis currently estimated to affect roughly 56 million people worldwide; the rate is expected to rise over 70 percent in the next 30 years.

“The study helps demystify gout for patients. There is a long-standing myth that gout is caused by diet. Our study emphasizes the importance of genetics,” Merriman said. “Diet only triggers gout attacks in people with an immune system primed to respond to urate crystals.”

Merriman believes the medical community needs to increase its general awareness of gout and its overall understanding of the condition.

“We know that high urate levels are an essential factor for gout, leading to the formation of urate crystals in joints and the immune reaction that causes gout. While there are gout treatments for reducing urate in the body and preventing gout, these treatments work in only about a third of people,” Merriman explained.

“There is an unmet clinical need in the prevention of gout in people with a propensity to flare and better treatment of the flare,” Merriman said. “Current treatments can be toxic if used in a prolonged way. It is important to understand gout flare mechanisms.”

Merriman’s research may hold insights for additional illnesses and disorders.

“The central gout flare effector is a very intense activation of the NLRP3 inflammasome, a piece of molecular machinery in the immune system that churns out the cytokine interleukin-1beta in response to urate crystals,” Merriman said.

“In other conditions, like heart and kidney disease, the NLRP3 inflammasome is also activated. These conditions may benefit from the knowledge of this gout genome-wide association study,” he continued.

Merriman’s research interests also include outcomes in gout, especially severity and drug response. He also applies genetic epidemiological techniques to understanding the causal relationships in gout, specifically of diet to hyperuricemia, and of gout to related co-morbidities.

“Genes with inherited genetic variants that associate with gout define those genes and the pathways they work in as causal pathways in gout, which can be targeted to develop new therapies,” Merriman said.

These approaches have an immediate impact on clinical practice, such as the role of diet in management approaches, and implications for longer-term management of gout by potentially identifying drug targets.

“All these genes and pathways can now be followed up to develop therapies. There is also the possibility of repurposing FDA-approved drugs used in other diseases based on the new targets we identified,” Merriman said.