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

Abstract

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 1 mg/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.

Keywords:

• Epidemiology
• risk
• biomarkers

Acknowledgments

Drs. O’Reilly and Ascherio had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. We would like to acknowledge the cohorts’ participants and Leslie Unger for administrative support.

Declaration of interest

The following authors report no conflicts of interest: Éilis J. O’Reilly, Kjetil Bjornevik, Marjorie L. McCullough, Laurence N. Kolonel, Loic Le Marchand, JoAnn E. Manson, and Alberto Ascherio.

Michael A. Schwarzschild was Funded by Target ALS.

This work was supported by a grant from the National Institute of Neurological Diseases and Stroke (R01 NS045893) awarded to AA. The NHS is funded by the National Institute Health through grants UM1 CA186107 and R01 CA49449. The HPFS cohort is funded by the National Institute Health through grant UM1 CA167552. The American Cancer Society funds the creation, maintenance and updating of the CPS-II cohorts. The MEC cohort is funded by the National Institute Health through U01 CA164973. The WHI program is funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, U.S. Department of Health and Human Services through contracts, HHSN268201600018C, HHSN268201600001C, HHSN268201600002C, HHSN268201600003C, and HHSN268201600004C.

MAS is funded by grants from Target ALS. The sponsors had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript.