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The genetics of hyperuricaemia and gout.
Nat Rev Rheumatol. 2012 Oct; 8(10):610-21.NR

Abstract

Gout is a common and very painful inflammatory arthritis caused by hyperuricaemia. This review provides an update on the genetics of hyperuricaemia and gout, including findings from genome-wide association studies. Most of the genes that associated with serum uric acid levels or gout are involved in the renal urate-transport system. For example, the urate transporter genes SLC2A9, ABCG2 and SLC22A12 modulate serum uric acid levels and gout risk. The net balance between renal urate absorption and secretion is a major determinant of serum uric acid concentration and loss-of-function mutations in SLC2A9 and SLC22A12 cause hereditary hypouricaemia due to reduced urate absorption and unopposed urate secretion. However, the variance in serum uric acid explained by genetic variants is small and their clinical utility for gout risk prediction seems limited because serum uric acid levels effectively predict gout risk. Urate-associated genes and genetically determined serum uric acid levels were largely unassociated with cardiovascular-metabolic outcomes, challenging the hypothesis of a causal role of serum uric acid in the development of cardiovascular disease. Strong pharmacogenetic associations between HLA-B*5801 alleles and severe allopurinol-hypersensitivity reactions were shown in Asian and European populations. Genetic testing for HLA-B*5801 alleles could be used to predict these potentially fatal adverse effects.

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Authors+Show Affiliations

Reginato AM
Rheumatology Division, Rhode Island Hospital, The Warren Alpert Medical School of Brown University, 593 Eddy Street Street, Providence, RI 02903, USA.
Mount DB
No affiliation info available
Yang I
No affiliation info available
Choi HK
No affiliation info available

MeSH

ATP Binding Cassette Transporter, Subfamily G, Member 2ATP-Binding Cassette TransportersAllopurinolGlucose Transport Proteins, FacilitativeGoutGout SuppressantsHumansHyperuricemiaNeoplasm ProteinsOrganic Anion TransportersOrganic Cation Transport ProteinsUric Acid

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Review

Language

eng

PubMed ID

22945592

Citation

Reginato, Anthony M., et al. "The Genetics of Hyperuricaemia and Gout." Nature Reviews. Rheumatology, vol. 8, no. 10, 2012, pp. 610-21.
Reginato AM, Mount DB, Yang I, et al. The genetics of hyperuricaemia and gout. Nat Rev Rheumatol. 2012;8(10):610-21.
Reginato, A. M., Mount, D. B., Yang, I., & Choi, H. K. (2012). The genetics of hyperuricaemia and gout. Nature Reviews. Rheumatology, 8(10), 610-21. https://doi.org/10.1038/nrrheum.2012.144
Reginato AM, et al. The Genetics of Hyperuricaemia and Gout. Nat Rev Rheumatol. 2012;8(10):610-21. PubMed PMID: 22945592.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The genetics of hyperuricaemia and gout. AU - Reginato,Anthony M, AU - Mount,David B, AU - Yang,Irene, AU - Choi,Hyon K, Y1 - 2012/09/04/ PY - 2012/9/5/entrez PY - 2012/9/5/pubmed PY - 2013/3/21/medline SP - 610 EP - 21 JF - Nature reviews. Rheumatology JO - Nat Rev Rheumatol VL - 8 IS - 10 N2 - Gout is a common and very painful inflammatory arthritis caused by hyperuricaemia. This review provides an update on the genetics of hyperuricaemia and gout, including findings from genome-wide association studies. Most of the genes that associated with serum uric acid levels or gout are involved in the renal urate-transport system. For example, the urate transporter genes SLC2A9, ABCG2 and SLC22A12 modulate serum uric acid levels and gout risk. The net balance between renal urate absorption and secretion is a major determinant of serum uric acid concentration and loss-of-function mutations in SLC2A9 and SLC22A12 cause hereditary hypouricaemia due to reduced urate absorption and unopposed urate secretion. However, the variance in serum uric acid explained by genetic variants is small and their clinical utility for gout risk prediction seems limited because serum uric acid levels effectively predict gout risk. Urate-associated genes and genetically determined serum uric acid levels were largely unassociated with cardiovascular-metabolic outcomes, challenging the hypothesis of a causal role of serum uric acid in the development of cardiovascular disease. Strong pharmacogenetic associations between HLA-B*5801 alleles and severe allopurinol-hypersensitivity reactions were shown in Asian and European populations. Genetic testing for HLA-B*5801 alleles could be used to predict these potentially fatal adverse effects. SN - 1759-4804 UR - https://www.unboundmedicine.com/medline/citation/22945592/The_genetics_of_hyperuricaemia_and_gout_ L2 - https://doi.org/10.1038/nrrheum.2012.144 DB - PRIME DP - Unbound Medicine ER -