4 January 2013
A large-scale study has identified 18 new gene regions (loci) linked to risk of developing gout.
The research combined data from more than 140,000 individuals and found 28 significantly associated loci in total, confirming all previously reported associations as well as uncovering the 18 new ones. Whereas most of the previously known loci mapped to genes that encode proteins involved in transporting uric acid or urate into and out of cells, none of the newly-found loci appear to be directly involved in urate transport.
Gout results from excess uric acid in the blood which crystallises, forming deposits in joints and surrounding tissue that lead to swelling and (often intense) pain. The condition affects nearly 1 million people in the UK and is the most common form of inflammatory arthritis. Whether or not it afflicts a particular individual is influenced by a complex interplay between genetic and lifestyle factors.
Most of the newly identified loci appear to be connected to regulatory pathways, in particular to those involved in glucose metabolism and to the inhibins-activins pathway which mediates a vast range of processes. The study authors speculate on the means by which alterations in these pathways might affect concentration of uric acid in blood serum, and the potential therapeutic targets they may present.
Current therapies for gout have variable response rates and can sometime have serious side effects. This work could ultimately help the development of new and improved methods for the treatment and prevention of the disease, although further and more detailed investigation of the mechanisms involved will first be required.