A study led by a team of scientists in Scotland suggests that genes may play a part in increasing one’s risk of developing gout, a painful condition that affects the joints.

The study is published in the 9 March online issue of Nature Genetics and is the work of researchers based at the MRC Human Genetics Unit, Western General Hospital, Edinburgh, and colleagues from other research centres in the UK and also in Croatia and Germany.

Gout (also called metabolic arthritis) is a painful condition caused when uric acid, a waste product of purine metabolism that in humans and great apes is mostly excreted via the kidneys into urine, deposits in the joints.

In some people the kidneys don’t clear all the uric acid from the bloodstream, a condition that is called hyperuricemia.

Some 10 per cent of people with hyperuricemia go on to develop gout, where uric acid is deposited in the joints as monosodium urate crystals, resulting in inflammation and often considerable pain. The condition usually affects the joint of the big toe, but it can also affect fingers, elbows, ankles, knees and other joints.

Causes of gout have often been attributed to diet and lifestyle, with overconsumption of protein, refined sugar and alcohol being the main culprits, but the mystery that has remained is why thousands of people with these lifestyles don’t develop gout.

The answer, according to this study, could be genetic. The researchers studied the genes of more than 12,000 people and found that a gene variant may increase or lower the risk of a person developing gout.

The gene variant in question is called SLC2A9, already known to scientists as a transporter of fructose, but in this new study, the researchers, led by Professor Alan Wright of the MRC Human Genetics Unit, found the variant also plays a key role in transporting uric acid.

Wright and colleagues found that between 1.7 and 5.3 per cent of the variance in blood levels of uric acid was explained by the presence of this gene variant in a Croatian population sample, and that SLC2A9 was also linked with low levels of uric acid excretion and/or gout in population samples from the UK, Croatia and Germany.

The presence of the gene variant appears to impede the ability of the kidneys to filter uric acid from the bloodstream.

According to a BBC News report, Wright said that:

“The gene is a key player in determining the efficiency of uric acid transport across the membranes of the kidney.”

The level of risk that a person has for gout will depend on which form of the gene they have inherited, said the researchers, who hope this discovery will lead to the development of improved diagnostics for the condition.

The traditional view of gout is often associated with historical stereotypes of overindulgent people who eat and drink to excess, but in reality this often not the case, with estimates placing about 1 million people in the UK suffering from some form of gout.

A representative of the British Society for Rheumatology, Professor Stuart Ralston told the BBC that he often saw people with gout who did not fit the stereotype of excessive drinking and eating of rich food, saying he knew of many patients that were “quite abstemious”. Perhaps this study reveals a genetic marker for gout risk, he said, and that it could be a “target for new gout drugs”. There are few medications that treat gout.

Another expert told BBC News there appears to be a link between this study and another one that suggested excessive drinking of sugary soft drinks also increased the risk of gout, since the gene variant that appears to control the ability of the body to remove uric acid from the blood is the same one that transports fructose, a sugar often found in soft drinks.

“SLC2A9 is a newly identified urate transporter influencing serum urate concentration, urate excretion and gout.
Veronique Vitart, Igor Rudan, Caroline Hayward, Nicola K Gray, James Floyd, Colin NA Palmer, Sara A Knott, Ivana Kolcic, Ozren Polasek, Juergen Graessler, James F Wilson, Anthony Marinaki, Philip L Riches, Xinhua Shu, Branka Janicijevic, Nina Smolej-Narancic, Barbara Gorgoni, Joanne Morgan, Susan Campbell, Zrinka Biloglav, Lovorka Barac-Lauc, Marijana Pericic, Irena Martinovic Klaric, Lina Zgaga, Tatjana Skaric-Juric, Sarah H Wild, William A Richardson, Peter Hohenstein, Charley H Kimber, Albert Tenesa, Louise A Donnelly, Lynette D Fairbanks, Martin Aringer, Paul M McKeigue, Stuart H Ralston, Andrew D Morris, Pavao Rudan, Nicholas D Hastie, Harry Campbell and Alan F Wright.
Nature Genetics Published online: 09 March 2008

Click here for Abstract.

Sources: Journal abstract, BBC News.

Written by: Catharine Paddock, PhD