The genetics of gout: translation into clinical practice

Gout results from an innate immune response to monosodium urate crystals deposited in joints in people with hyperuricemia. Central to this is activation of the NLRP3 inflammasome and secretion of interleukin-1β. The pathogenic mechanism of NLRP3 inflammasome activation in gout is not well understood...

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Bibliographic Details
Main Authors: Tony R. Merriman, Fiorella Rosas-Chavez, Lisa K. Stamp
Format: Article
Language:English
Published: SAGE Publishing 2025-08-01
Series:Therapeutic Advances in Musculoskeletal Disease
Online Access:https://doi.org/10.1177/1759720X251366360
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Summary:Gout results from an innate immune response to monosodium urate crystals deposited in joints in people with hyperuricemia. Central to this is activation of the NLRP3 inflammasome and secretion of interleukin-1β. The pathogenic mechanism of NLRP3 inflammasome activation in gout is not well understood. However, recent genome-wide association studies (GWAS) in gout have revealed new pathogenic pathways, for example, genes involved in NLRP3 inflammasome activation and activity, and genes involved in clonal hematopoiesis of indeterminate potential. Genetic risk variants identified by GWAS are being used in Mendelian randomization studies to understand putative causal relationships between gout and co-morbid conditions (e.g., insulin resistance is causal of hyperuricemia). The genetic risk variants can also be combined into a genetic risk score to predict outcome in gout. Finally, inherited genetic variants influence response to allopurinol, in particular the p.Gln141Lys variant in ABCG2.
ISSN:1759-7218