Pre-diagnostic plasma urate and the risk of amyotrophic lateral sclerosis

Objective: To prospectively examine for the first time the association between plasma urate levels measured in healthy participants and future amyotrophic lateral sclerosis (ALS) risk.Methods: A pooled case-control study nested in five US prospective cohorts comprising 319,617 participants who provided blood, of which 275 had ALS during follow-up. Pre-diagnostic plasma urate was determined for all participants using a clinical colorimetric enzyme assay. Gender-specific multivariable-adjusted rate ratios (RR) of ALS incidence or death estimated by conditional logistic regression and pooled using inverse-variance weighting.Results: In age- and matching factor-adjusted analyses, a 1mg/dL increase in urate concentration was associated with RR=0.88 (95% CI: [0.78, 0.997] p=0.044). After adjustment for BMI, a strong predictor of ALS and urate levels, and other potential covariates, the RR=0.89 (95% CI: [0.78, 1.02]; p=0.08 for 1mg/dL increase in urate).Conclusion: Elevation of plasma urate was modestly inversely associated with the risk of ALS and warrants further study for a potential role in this disease.