Éilis J O'Reilly1,2, Kjetil Bjornevik3,4, Michael A Schwarzschild5, Marjorie L McCullough6, Laurence N Kolonel7, Loic Le Marchand7, Joann E Manson8,9, Alberto Ascherio2,9,10. 1. a School of Public Health , College of Medicine, University College Cork , Cork , Ireland. 2. b Department of Nutrition , Harvard TH Chan School of Public Health , Boston , MA , USA. 3. c Department of Global Public Health and Primary Care , University of Bergen , Bergen , Norway. 4. d The Norwegian Multiple Sclerosis Competence Center, Department of Neurology , Haukeland University Hospital , Bergen , Norway. 5. e Department of Neurology , Massachusetts General Hospital , Boston , MA , USA. 6. f Epidemiology Research Program , American Cancer Society , Atlanta , GA , USA. 7. g Epidemiology Program , University of Hawaii Cancer Center , Honolulu , HI , USA. 8. h Department of Medicine Brigham and Women's Hospital , Harvard Medical School , Boston , MA , USA. 9. i Department of Epidemiology , Harvard TH Chan School of Public Health , Boston , MA , USA , and. 10. j Channing Division of Network Medicine , Brigham and Women's Hospital and Harvard Medical School , Boston , MA , USA.
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.
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.
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