Document Detail

The genetics of hyperuricaemia and gout.
MedLine Citation:
PMID:  22945592     Owner:  NLM     Status:  MEDLINE    
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.
Anthony M Reginato; David B Mount; Irene Yang; Hyon K Choi
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Review     Date:  2012-09-04
Journal Detail:
Title:  Nature reviews. Rheumatology     Volume:  8     ISSN:  1759-4804     ISO Abbreviation:  Nat Rev Rheumatol     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-01     Completed Date:  2013-03-20     Revised Date:  2013-07-12    
Medline Journal Info:
Nlm Unique ID:  101500080     Medline TA:  Nat Rev Rheumatol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  610-21     Citation Subset:  IM    
Rheumatology Division, Rhode Island Hospital, The Warren Alpert Medical School of Brown University, 593 Eddy Street Street, Providence, RI 02903, USA.
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MeSH Terms
ATP-Binding Cassette Transporters / genetics
Allopurinol / adverse effects
Glucose Transport Proteins, Facilitative / genetics
Gout / drug therapy,  genetics*
Gout Suppressants / adverse effects
Hyperuricemia / genetics*
Neoplasm Proteins / genetics
Organic Anion Transporters / genetics
Organic Cation Transport Proteins / genetics
Uric Acid / blood
Grant Support
Reg. No./Substance:
0/ABCG2 protein, human; 0/Glucose Transport Proteins, Facilitative; 0/Gout Suppressants; 0/Neoplasm Proteins; 0/Organic Anion Transporters; 0/Organic Cation Transport Proteins; 0/SLC22A12 protein, human; 0/SLC2A9 protein, human; 315-30-0/Allopurinol; 69-93-2/Uric Acid

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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