Researchers have decoded a genetic variant that enables new understanding of why some people are at risk of gout, a painful and debilitating arthritic disease.
Gout is caused by persistently elevated levels of urate in the blood, which causes severe joint pain and swelling, especially in peoples' toes, knees, elbows, wrists and fingers.
It can be treated using drugs that lower urate levels. But if left untreated, it can cause serious damage to joints, kidneys and quality of life.
A team from the University of Otago in New Zealand, characterised the genetic variant that lies not inside, but just next to a gene called PDZK1 -- which helps excrete urate through the kidney and gut.
In this way, PDZK1 controls the amount of serum urate which, when high, form crystals that cause gout.
"We found that the genetic variant doesn't affect the PDZK1 protein, but causes change in the amount of the PDZK1 gene produced," said Julia Horsfield, Associate Professor at the varsity.
"Unexpectedly, the effect of the genetic variant in humans is in the gut as well as the kidney.
"Our results have identified a new molecular pathway for gout, enabling new understanding of why there is gout risk in patients with this particular genetic variant," Horsfield said.
The research, published in the journal Human Molecular Genetics, showed that there are dozens of regions in the human genome with signals that increase serum urate levels and risk of gout, and kidney function.
However, the new challenge is converting these signals into functional insights as it can allow new medical intervention in gout and kidney disease.
"Since many of the regions lie outside of genes, it is not known how they could control urate levels and risk of gout or kidney disease. These associated regions probably represent regulatory elements that control gene expression," Horsfield said.