Substantial Genetic Contribution to Hyperuricemia and Gout

International team of scientists makes important contribution to improve understanding of uric acid metabolism and gout – publication in the journal “Nature Genetics”

What leads to elevated blood concentrations of uric acid, as often seen in patients with gout?  And how do elevated uric acid concentrations contribute to the development of gout? An international team of scientists could make an important contribution to help answer these questions. It has long been observed that elevated uric acid concentrations and gout can run in families. By studying the genetic information of 140,000 study participants, a large team of 220 scientists who collaborate in the international “Global Urate Genetics Consortium” (GUGC) were now able to identify 28 genetic risk variants for elevated blood concentrations of uric acid.

To accomplish this task, the scientists employed state-of-the-art methods that can be used to systematically survey the entire genome for such genetic risk variants. The identified genetic variants that were associated with elevated uric acid levels were also clearly associated with an increased risk for gout. Gout is a metabolic disease that can develop when uric acid crystals precipitate in joints. It affects about 2% of the population in industrialized countries. Gout attacks are extremely painful, and chronic gout can lead to permanent joint damage.

The study, which is published online ahead of print in Nature Genetics on December 23, combines data from more than 70 individual studies from Europe, the U.S., Japan and Australia and represents the largest study worldwide on this topic.

“I very much enjoy working in a large international team,” says professor Terho Lehtimäki. "Our work is organized in weekly telephone conferences, and we try to meet in person at international scientific meetings. This kind of work is only made possible by a great deal of teamwork and the voluntary participation of thousands of participants in such studies”.

A novel insight from the study was that the genetic risk variants do not only increase blood uric acid concentrations by reducing its excretion from the body, but also by altering the rate of uric acid production and its metabolism. As a next step, the scientists want to gain more insights into the molecular mechanisms underlying an increased susceptibility to gout. These mechanisms can serve as a starting point for the development of novel therapies to treat gout, or to improve the diagnosis and prevention of chronic gout.

Citation: Köttgen, Albrecht, Teumer, Vitart, Krumsieket al, 2012. Nature Genetics, doi:10.1038/ng.2500

For further information please contact
Professor Terho Lehtimäki, +358 50 433 6285, terho.lehtimaki@uta.fi