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

Abstract

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; ptrend = 0.049) in men and 1.04 (95% CI 0.61, 1.78; ptrend = 0.44) in women (pheterogeneity = 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.

Figure. Pooled relative risks (RRs) of Parkinson disease (PD) for the highest vs lowest quartiles of plasma/serum urate concentrations in men and women in the meta-analysis

(A) Men. (B) Women. Pooled RR was 0.63 (95% confidence interval [CI] 0.42, 0.95; p = 0.03; p_{heterogeneity} = 0.22) in men and 0.89 (95% CI 0.57, 1.40; p = 0.61; p_{heterogeneity} = 0.52) in women. In the Health Professionals Follow-up Study (HPFS) cohort, 84 out of 162 PD cases were included in a previous case-control study (reference 5), and in the Nurses' Health Study (NHS) cohort, 101 out of 156 PD cases were included in a previous case-control study (reference 7). CPS IIN = Cancer Prevention Study II Nutrition.