杏吧原创

Almost 400 genetic variants have been linked to gout in the largest study of its kind.

Gout is a type of arthritis that leads to painful flare-ups around joints. The condition is caused by a build-up of uric acid, or urate, from the breakdown of molecules called purines. This causes urate crystals to form in joints, leading to a painful inflammatory response.

Purines are made in the body and found in certain foods and drinks, such as bacon and beer. Drinking alcohol in moderation and limiting fatty foods can reduce the risk of gout, however, researchers at the University of Otago in New Zealand wanted to better understand the role of genetics in the condition.

To learn more, and his colleagues analysed the genomes of over 120,000 people with known or suspected gout and 2.5 million people without such a diagnosis or any symptoms of the condition. The researchers described the participants鈥� ancestry as being African, East Asian, European or Latinx, meaning people of Latin American ancestry.

The team identified 376 genetic variants that are linked to gout, of which 148 had not previously been associated with the condition.

Some of these genetic regions are involved in adding and removing molecular markers on DNA.

鈥淲e provide evidence that genetic variants linked to remodelling of DNA do causally influence gout risk,鈥� says Merriman.

Further analysis by the team suggests that in men, but not women, gout is also linked to genetic variants that control the activity of a gene that encodes the enzyme xanthine dehydrogenase, which makes uric acid.

Results suggest these variants regulate xanthine dehydrogenase鈥檚 activity in the prostate, which may explain why gout is roughly four times more common in men than women, says Merriman.

In experiments in male mice, the team found that urate was in the animals鈥� prostates at levels similar to the liver, which is widely considered the main producer of urate.

Urate has antioxidant properties and has been found in semen, therefore prostates may make it to protect sperm cells from damaging molecules, says Merriman. Some men produce excessive amounts of urate, leading to gout.

In another part of the study, the team used this genetic variant information to predict the gout risk of more than 332,000 people of European descent, some of whom had gout. When the researchers compared this information with known or suspected gout cases, the risk score generally performed well and was slightly more accurate than when a person鈥檚 gout risk was gauged by factors like their age or sex, says Merriman.

The first part of the study was made up of participants of several ethnic backgrounds, however, most were of European ancestry, says Merriman. 鈥淲e need more data for people of non-European ancestry, because that is how we can reduce health inequity,鈥� he says. The team is now studying the genetic links to gout in a larger group of people of African descent, he says.

鈥淭his study will significantly add to our understanding of the genetics of gout risk and may provide a road map to pathways that can be targeted for new gout therapies,鈥� says at the University of Maryland. In the meantime, further studies are required to confirm a potential link between these genetic variants and gout, he says.