Dose-response meta-analysis on urate, gout, and the risk for Parkinson's disease

Abstract

The relationship between Parkinson's disease (PD) and urate or gout has attracted significant interest in recent years, but the results were conflicting. This dose-response meta-analysis aimed to estimate the correlation between urate levels or gout and the risk for PD. The Embase, PubMed, and Medline databases were searched for studies that investigated the relationship between the risk for PD and urate levels or gout. Random-effects or fixed-effects models were used to obtain pooled relative risks (RRs) and corresponding 95% confidence intervals (CIs). Fifteen studies, involving 449,816 participants and 14,687 cases in total, were included in the meta-analysis. High serum urate levels were associated with decreased risk for PD (RR 0.44 [95% CI 0.32-0.55]). Subgroup analysis according to sex revealed a neuroprotective effect of high urate levels against PD among females (0.68 [95% CI 0.43-0.93]) and males (0.49 [95% CI 0.34-0.64]). The risk for PD was lowered by 6% (0.94 [95% CI 0.90-0.98]) for each 1 mg/dl increase in serum urate level and reduced by 13% (0.87 [95% CI 0.80-0.95]) with each 2 mg/dl increase in serum urate level. However, gout was not closely correlated with the risk for PD (0.97 [95% CI 0.85-1.09]). Higher serum urate levels reduced the risk for PD, which was decreased by 6% (relative risk reduction) for each 1 mg/dl increase in serum urate levels. And the results indicated that urate may exert protective effects against the development of PD.

Fig. 1. Flow diagram showing the selection process of articles.

15 studies were included in the meta-analysis.

Fig. 2. RRs with 95% CIs from studies on the correlation between high urate concentration and risks of PD.

The adjusted pooled estimate was 0.44 (95% CI 0.32–0.55).

Fig. 3. Sensitivity analysis omitting one article in turn from the analyses on the correlation between high urate concentration and PD risks.

The vertical lines show the summary estimate (0.49) and its 95% CI (0.18–0.81) from the meta-analysis of all the articles.

Fig. 4. Subgroup analyses by sex on the correlation between urate concentration and PD risk.

RRs were 0.68 (95% CI 0.43–0.93) in females and 0.49 (95% CI 0.34–0.64) in males.

Fig. 5. Dose–response correlation between urate levels and PD risk.

Restricted cubic spline revealed a negative linear correlation.

Fig. 6. RRs with 95% CIs from studies on the correlation between gout and PD risk.

The pooled estimate was 0.97 (95% CI 0.85–1.09).

Fig. 7. Sensitivity analysis omitting each study in turn from the analyses on the correlation between gout and the risk of PD.

The vertical lines show the summary estimate (0.88) and its 95% CI (0.21–1.55) from the meta-analysis of all the articles.

Fig. 8. Subgroup analyses by sex on the association between gout and PD risk.

RRs were 0.97 (95% CI 0.78–1.16) in females and 0.88 (95% CI 0.71–1.04) in males.