The genetic basis of hyperuricaemia and gout

Joint Bone Spine. 2011 Jan;78(1):35-40. doi: 10.1016/j.jbspin.2010.02.027. Epub 2010 May 15.


Gout results from elevated urate concentrations in the blood (hyperuricaemia). When super-saturation of urate is reached, monosodium urate crystals form within the joint. In some individuals, these crystals elicit a painful self-limiting inflammatory response that is characteristic of acute gouty arthritis. The most important cause of hyperuricaemia is reduced excretion of uric acid in the urine. Uric acid excretion is coordinated by a suite of urate transport molecules expressed in the renal collecting tubules, and is a key physiological checkpoint in gout. Other checkpoints in gout are hepatic production of urate, monosodium urate crystal formation, and initiation of the acute inflammatory response. Genome-wide association scans for genes regulating serum urate concentrations have identified two major regulators of hyperuricaemia- the renal urate transporters SLC2A9 and ABCG2. The risk variants at each gene approximately double the risk for gout in people of Caucasian ancestry, with SLC2A9 also resulting in higher risk for gout in people of Polynesian ancestry, a diverse population characterized by a high prevalence of gout. Ongoing genetic association studies are identifying and confirming other genes controlling serum urate concentrations; although genome-wide association studies in gout per se await recruitment of suitable case sample sets.

Publication types

  • Review

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • ATP-Binding Cassette Transporters / genetics*
  • Glucose Transport Proteins, Facilitative / genetics*
  • Gout / ethnology
  • Gout / genetics*
  • Humans
  • Hyperuricemia / ethnology
  • Hyperuricemia / genetics*
  • Neoplasm Proteins / genetics*


  • ABCG2 protein, human
  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • ATP-Binding Cassette Transporters
  • Glucose Transport Proteins, Facilitative
  • Neoplasm Proteins
  • SLC2A9 protein, human