Faculty, Staff and Student Publications
Publication Date
9-1-2023
Journal
Arthritis & Rheumatology
Abstract
OBJECTIVE: To prospectively investigate population-based metabolomics for incident gout and reproduce the findings for recurrent flares, accounting for serum urate.
METHODS: We conducted a prediagnostic metabolome-wide analysis among 105,615 UK Biobank participants with nuclear magnetic resonance metabolomic profiling data (168 total metabolites) from baseline blood samples collected 2006-2010 in those without history of gout. We calculated hazard ratios (HRs) for incident gout, adjusted for gout risk factors, excluding and including serum urate levels, overall and according to fasting duration before sample collection. Potential causal effects were tested with 2-sample Mendelian randomization. Poisson regression was used to calculate rate ratios (RRs) for the association with recurrent flares among incident gout cases.
RESULTS: Correcting for multiple testing, 88 metabolites were associated with risk of incident gout (N = 1,303 cases) before serum urate adjustment, including glutamine and glycine (inversely), and lipids, branched-chain amino acids, and most prominently, glycoprotein acetyls (GlycA; P = 9.17 × 10
CONCLUSION: This prospective, population-based study implicates GlycA, a stable long-term biomarker reflecting neutrophil overactivity, in incident and recurrent gout flares (central manifestation from neutrophilic synovitis) beyond serum urate.
Keywords
Humans, Uric Acid, Prospective Studies, Mendelian Randomization Analysis, Gout, Risk Factors, Glycoproteins
DOI
10.1002/art.42523
PMID
37043280
PMCID
PMC10524152
PubMedCentral® Posted Date
9-1-2024
PubMedCentral® Full Text Version
Author MSS
Published Open-Access
yes