7 Aug 2014

Genetics of Gout

From Our Changing World, 9:34 pm on 7 August 2014

Gout is a form of arthritis caused by high levels of uric acid in the blood. In some people, high uric acid levels form solid crystals in the joints, and arthritis results when the immune system reacts in a very painful way against those crystals.

Long thought of as a disease of affluent males, gout affects a wide range of people and its rates are increasing. In New Zealand, roughly 3% of European adults, between 6-7% of Maori adults and nearly 8% of Pacifica adults have gout. The incidence is much higher among males, although the rate increases among post-menopausal women.

Tony Merriman is a biochemist at the University of Otago, and an expert in the genetics and epidemiology of gout.

“We know that genes are important in determining who gets gout and who doesn’t, but environment is equally important because how we live and what we eat modulates the overall level of gout in a country,” says Tony.

Foods that raise uric acid levels are high purine foods such as seafood, red meat and alcohol. Recently, tomato has been shown to raise uric acid levels. Individual people react differently to different foods, depending on their underlying genetic disposition.

Recent research shows a strong link between the intake of sugar, especially sugary drinks, and the incidence of gout. Some genes implicated in gout have already been identified, and work shows that they can interact with food in complex ways.

“There’s one gene that’s very important in gout,” says Tony. “And it’s involved in getting rid of uric acid through the kidneys and the urine. It’s a transporter for uric acid, but one of the other things it transports is fructose … So what we find with the gene is that there’s one particular variant or allele that protects people from gout, and is very good at getting rid of uric acid. But when this particular variant sees sugar it completely flip-flops and does the opposite. It seems to keep more uric acid from urine and increase the chances of gout. So what we can say is that people with a certain genotype will react more badly to sugar than people with the other genotype.”

Tony is involved in an international collaboration called ‘Eurogout’, and was recently awarded a Health Research Council grant to begin a genome-wide scan looking for genes associated with gout, using samples collected from thousands of people with different ancestry.

“We’re trying to understand the genes,” says Tony, “And we do that by comparing DNA between people with and without gout, and linking that with information about diet.”

PhD student Anna Gosling is a biological anthropologist working with Tony and with Lisa Matisoo-Smith, and she is investigating how the history of Maori and Pacifica people has contributed to high urate levels in their populations. Recent research shows that a high incidence of gout is not just a recent phenomena, and one hypothesis is that high levels of urate may have provided protection against malaria.

Te Ahi Kaa recently featured gout and the experiences of Maori suffering from gout.

Genetics of Gout

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