Gene could spell new chapter in fight against gout

Mar 10 2008

Researchers have found why some people are more susceptible to gout than others. The scientists looked at the genetic codes of more than 12,000 people after identifying a gene linked to uric acid levels in the blood.

The work by the Medical Research Council Human Genetics Unit in collaboration with the University of Edinburgh and Croatian scientists shows that a known sugar transporter, called SLC2A9, is mainly responsible for the transport of uric acid within the body. Variations in the gene that codes for this transporter cause some people to have higher levels of uric acid in their blood than others. Uric acid build-up can lead to gout, a common, painful disease marked by inflammation of joints. The findings are published in Nature Genetics.

Looking at different populations in Croatia, Orkney, and Tayside, the team identified genetic variations in the SLC2A9 gene, which accounted for differences in uric acid levels. They carried out further tests and ruled out connections between variations of this gene and increased risks of heart disease, obesity and raised blood pressure. Further work with researchers in Germany helped to show that the gene is associated with kidney function, in particular the capacity to remove uric acid from the body through the urine.

Professor Alan Wright of the MRC Human Genetics Unit and one of the lead authors of the paper, said: “This finding allows us to understand a new and important mechanism by which uric acid is transported and provides a means of clarifying the role of uric acid in a range of diseases. The gene is a key player in determining the efficiency of uric acid transport across membranes of the kidney. Using frogs’ eggs as a model system allowed us to confirm that SLC2A9 is a uric acid transport protein.”

Harry Campbell, Professor of Genetic Epidemiology and Public Health at the University of Edinburgh and another senior author on the paper, added: “Some people will have higher or lower risk of gout depending on which form of the gene they inherited. This discovery may allow better diagnostic tools for gout to be developed.”

Professor Wright added: “The discovery of this important new function for the SLC2A9 protein will aid the development of drugs which could lower blood uric acid levels and prevent or treat gout.”

Original research paper: Vitart V et al. (2008). The major facilitator superfamily member SLC2A9 is a novel uric acid transporter influencing serum urate concentrations, urate excretion and gout. Nature Genetics.

Gout is the most common inflammatory arthritis in adult males. It is caused by high blood levels of uric acid. Uric acid crystals are deposited in the cartilage of joints, tendons and surrounding tissues and provoke an inflammatory reaction in these tissues. The condition causes burning pain, swelling, redness, warmness and stiffness in the affected joint.

Gout is more common in affluent societies due to a diet rich in refined sugars, proteins, and alcohol. Uric acid is formed from purine-rich foods such as seafood and from breakdown of the body’s own chemicals. The kidneys are responsible for most of the excretion of uric acid. (Most mammals have an enzyme to break down uric acid called uricase and so they have much lower blood levels but this enzyme is not found in humans.)