Gout and risk of Parkinson disease

Alonso, Álvaro; Rodrı́guez, Luis A. Garcı́a; Logroscino, Giancarlo; Hernán, Miguel A.

doi:10.1212/01.wnl.0000279518.10072.df

Cited by 154 publications

(155 citation statements)

References 29 publications

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“…25 Further, in a PD case-control study, participants carrying more genetic alleles associated with lower serum urate concentrations were more likely to have PD. 26 Individuals with gout, a chronic condition associated with hyperuricemia, have been also found to have lower risk of PD in 2 previous studies, 27,28 but not in a recent one. 29 Another possible interpretation for the observed urate-PD association is that urate may slow disease progression during the preclinical stage of PD.…”

Section: Resultsmentioning

confidence: 83%

Prospective study of plasma urate and risk of Parkinson disease in men and women

et al. 2016

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Objective: To examine whether higher plasma urate concentrations are associated with a lower risk of developing Parkinson disease (PD) and whether there is a sex difference in the potential urate-PD relationship. Methods:We conducted a nested case-control study based on 90,214 participants of 3 ongoing US cohorts. We identified 388 new PD cases (202 men and 186 women) since blood collection, which were then matched to 1,267 controls. PD cases were confirmed by medical record review. Conditional logistic regression estimated relative risks (RRs) and 95% confidence intervals (95% CIs), after adjustment for age, smoking, caffeine intake, plasma concentrations of cholesterol and ferritin, and other covariates. We also conducted a meta-analysis to combine our study with 3 previously published prospective studies on urate and PD risk. Results:In the present nested case-control study, the multivariate-adjusted RRs of PD comparing extreme quartiles of urate were 0.63 (95% CI 0.35, 1.10; p trend 5 0.049) in men and 1.04 (95% CI 0.61, 1.78; p trend 5 0.44) in women (p heterogeneity 5 0.001). In the meta-analysis, the pooled RRs comparing 2 extreme quartiles of urate were 0.63 (95% CI 0.42, 0.95) in men and 0.89 (95% CI 0.57, 1.40) in women. Conclusion:We observed that men, but not women, with higher urate concentrations had a lower future risk of developing PD, suggesting that urate could be protective against PD risk or could slow disease progression during the preclinical stage of disease. Urate is a potent antioxidant and contributes to approximately 60% of the free radical scavenging activity in human serum.1,2 Serum urate concentrations in humans and apes are many-fold higher than those in other mammals as a consequence of evolutionary urate oxidase gene mutations.1 Results from in vitro and in vivo experimental studies suggest that urate could be a potential neuroprotective agent via its capacity to modify the cerebral damage induced by reactive nitrogen and oxidative species.2,3 In most, 4-8 but not all, 9 prospective observational studies in humans, higher concentrations of plasma urate were associated with a lower risk of developing Parkinson disease (PD). Further, patients with PD with higher urate levels have been found to have a slower disease progression relative to those with lower urate concentrations. 10,11 However, significant associations of higher urate levels with lower PD risk and slower progression were observed only in men. [4][5][6][7][8][9] Studies relating blood urate levels to PD risk were limited by their small sample sizes (PD case number , 160 in all studies) and underrepresentation of women. Therefore, it remains unclear whether this sex difference reflects a true difference in underlying biology or is due to lack of statistical power because women generally have lower urate concentration and lower PD incidence compared with men. Further, only one previous study 7 controlled for plasma ferritin and cholesterol levels, which have been found to be

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Section: Resultsmentioning

confidence: 83%

Prospective study of plasma urate and risk of Parkinson disease in men and women

et al. 2016

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“…A large case-control study was performed within the General Practice Research Database, UK [663]. Previous gout was associated with lower risk of PD (OR 0.69, 95% CI 0.48-0.99), with the strongest associations among men, non-smokers and individuals above 60 years [663].…”

Section: Uric Acid and Goutmentioning

confidence: 99%

Epidemiology and etiology of Parkinson’s disease: a review of the evidence

et al. 2011

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“…History of gout is associated with reduced risk of developing either PD [48] or Alzheimer's disease [21]. Urate level determinants also modify susceptibility to PD.…”

Section: Urate and Its Determinants Are A Risk Factor For Neurodegenementioning

confidence: 99%

Urate as a Marker of Risk and Progression of Neurodegenerative Disease

Paganoni

Schwarzschild

2017

Neurotherapeutics

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Urate is a naturally occurring antioxidant whose levels are associated with reduced risk of developing Parkinson's disease (PD) and Alzheimer's disease. Urate levels are also associated with favorable progression in PD, amyotrophic lateral sclerosis, Huntington's disease, and multisystem atrophy. These epidemiological data are consistent with laboratory studies showing that urate exhibits neuroprotective effects by virtue of its antioxidant properties in several preclinical models. This body of evidence supports the hypothesis that urate may represent a shared pathophysiologic mechanism across neurodegenerative diseases. Most importantly, beyond its role as a molecular predictor of disease risk and progression, urate may constitute a novel therapeutic target. Indeed, clinical trials of urate elevation in PD and amyotrophic lateral sclerosis are testing the impact of raising peripheral urate levels on disease outcomes. These studies will contribute to unraveling the neuroprotective potential of urate in human pathology. In parallel, preclinical experiments are deepening our understanding of the molecular pathways that underpin urate's activities. Altogether, these efforts will bring about new insights into the translational potential of urate, its determinants, and its targets and their relevance to neurodegeneration.

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Gout and risk of Parkinson disease

Abstract: Gout is associated with a lower risk of Parkinson disease (PD). Our findings provide additional support for a potential link between uric acid and PD. Further research is required to explore a potential effect modification by sex.

Cited by 154 publications

References 29 publications

Prospective study of plasma urate and risk of Parkinson disease in men and women

Prospective study of plasma urate and risk of Parkinson disease in men and women

Epidemiology and etiology of Parkinson’s disease: a review of the evidence

Urate as a Marker of Risk and Progression of Neurodegenerative Disease

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