Prediagnostic Amino Acid Metabolites and Risk of Gout, Accounting for Serum Urate: Prospective Cohort Study and Mendelian Randomization
Authors' conclusion
These prospective findings with causal implications could lead to biomarker-based risk prediction and potential supplementation-based interventions with glycine or glutamine.
Study context
- Population
- UK Biobank participants without a history of gout, with NMR metabolomic profiling (168 metabolites, incl. 8 amino acids) of baseline blood samples (2006–2010)2,735 hospitalized gout cases
- Participants
- 249,677 participants
- Exposure
- Extreme quintiles of prediagnostic metabolites
- Outcome
- Incident hospitalized gout
Methodological detailsmetabolome-wide analysis, nuclear magnetic resonance metabolomic profiling, multivariable Cox hazard ratios (HRs) before and after serum urate adjustment, correction for multiple testing
- Metabolome-wide analysis
- Nuclear magnetic resonance metabolomic profiling
- Multivariable Cox HRs before and after serum urate adjustment
- Correction for multiple testing
Main finding
As reported in the abstract
Incident hospitalized gout, extreme quintiles of metabolite
- Metabolites associated with hospitalized gout before urate adjustment (after multiple-testing correction)
- 107
- Glutamine, HR (extreme quintiles), before urate adjustment
- 0.64 (95% CI 0.54-0.75), P = 8.3 × 10-8
- Glycine, HR (extreme quintiles), before urate adjustment
- 0.69 (95% CI 0.61-0.78), P = 3.3 × 10-9
- Glycoprotein acetyls, HR, before urate adjustment
- 2.48 (95% CI 2.15-2.87), P = 1.96 × 10-34
- Glutamine, HR (extreme quintiles), after urate adjustment
- 0.83 (95% CI 0.70-0.98)
- Glycine, HR (extreme quintiles), after urate adjustment
- 0.86 (95% CI 0.76-0.98)
- Glycoprotein acetyls, HR (extreme quintiles), after urate adjustment
- 1.41 (95% CI 1.21-1.63)
Observational data: associations, not effects.
Further findings
Incident hospitalized gout per SD, after urate adjustment
- Glutamine, HR per SD
- 0.91 (95% CI 0.86-0.97)
- Glycine, HR per SD
- 0.94 (95% CI 0.91-0.98)
- Glycoprotein acetyls, HR per SD
- 1.10 (95% CI 1.06-1.14)
Sensitivity analysis including nonhospitalized incident gout
- Findings persisted when including patients with nonhospitalized incident gout
Mendelian randomization: urate levels and gout per SD of glycine and glutamine
- Glycine, change in urate per SD
- −0.05 mg/dL (95% CI −0.08 to −0.01)
- Glutamine, change in urate per SD
- −0.12 mg/dL (95% CI −0.22 to −0.03)
- Glycine, OR for gout
- 0.94 (95% CI 0.88-1.00)
- Glutamine, OR for gout
- 0.81 (95% CI 0.67-0.97)
Original publication
Prediagnostic Amino Acid Metabolites and Risk of Gout, Accounting for Serum Urate: Prospective Cohort Study and Mendelian Randomization. Arthritis Care Res (Hoboken). Published 16 October 2024. doi:10.
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