Plasma urate and risk of Parkinson's disease

Abstract

Oxidative stress contributes to dopaminergic neuron degeneration in Parkinson's disease. Urate, a potent antioxidant, could be neuroprotective. To determine whether higher plasma concentrations of urate predict a reduced risk of Parkinson's disease, the authors conducted a nested case-control study among participants in the Health Professionals Follow-up Study, a cohort comprising over 18,000 men who provided blood samples in 1993-1995. Eighty-four incident cases of Parkinson's disease were diagnosed through 2000, and each was randomly matched to two controls by year of birth, race, and time of blood collection. Rate ratios of Parkinson's disease according to quartile of uricemia were estimated by use of conditional logistic regression. The mean urate concentration was 5.7 mg/dl among cases and 6.1 mg/dl among controls (p = 0.01). After adjustment for age, smoking, and caffeine, the rate ratio of Parkinson's disease for the highest quartile of uricemia compared with the lowest was 0.43 (95% confidence interval: 0.18, 1.02; p(trend) = 0.017). This association was stronger in analyses excluding cases diagnosed within 4 years (median) from blood collection (rate ratio = 0.17, 95% confidence interval: 0.04, 0.69; p(trend) = 0.010). These results suggest that high plasma urate concentrations may decrease the risk of Parkinson's disease, and they raise the possibility that interventions to increase plasma urate may reduce the risk and delay the progression of Parkinson's disease.

Figure 1

Odds Ratios (OR) of Parkinson’s disease (PD) by quartile of urate concentration among controls adjusted for age, pack-years of smoking, and quintile of caffeine intake. OR are indicated next to the black diamonds and 95% confidence intervals are indicated by the vertical lines. A) All cases and controls, and B) Only cases whose blood was drawn more than 4 years before their PD diagnosis and their matched controls. The number of cases and controls in each quartile of urate concentration are shown below the figures.

Figure 1

Odds Ratios (OR) of Parkinson’s disease (PD) by quartile of urate concentration among controls adjusted for age, pack-years of smoking, and quintile of caffeine intake. OR are indicated next to the black diamonds and 95% confidence intervals are indicated by the vertical lines. A) All cases and controls, and B) Only cases whose blood was drawn more than 4 years before their PD diagnosis and their matched controls. The number of cases and controls in each quartile of urate concentration are shown below the figures.

Figure 2

A meta-analysis of cohort studies of Parkinson’s disease (PD). Rectangles indicate rate ratio ([RR] as estimated by the odds ratio in the present study) of PD corresponding to a 1.32 mg/dL (one standard deviation in the Health Professionals Follow-up Study [HPFS]) increase in the plasma concentration of urate in each study. The size of the rectangle is proportional to the percent weight of the corresponding RR in the meta-analysis; horizontal lines, representing the 95% CI, are plotted on a log scale. The pooled (combined) RR and 95% CI are indicated by the diamond. Urate in the Honolulu Heart Program (HHP) was determined twice, at the time of the first examination—about 30 years before the end of the follow-up—and at the third examination, six years after the first. Results in the figure are based on the third examination because results from the first examination are more likely to be attenuated by unaccounted changes in plasma urate during the follow-up. The pooled RR using results from the first examination would be 0.82 (95% CI: 0.71, 0.95; p = 0.0059). * p<0.0001.