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      Serum uric acid levels in patients with Parkinson’s disease: A meta-analysis

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          Abstract

          Background

          Lower serum uric acid (UA) levels have been reported as a risk factor in Parkinson’s disease (PD). However, the results have been inconsistent so far.

          Objectives

          The aim of the present study was to clarify the potential relationship of uric acid with PD.

          Methods

          Comprehensive electronic search in pubmed, web of science, and the Cochrane Library database to find original articles about the association between PD and serum uric acid levels published before Dec 2015. Literature quality assessment was performed with the Newcastle-Ottawa Scale. Random-effects model was used to estimate the standardized mean differences (SMDs) with 95% confidence intervals (CIs). Heterogeneity across studies was assessed using I 2 and H 2 statistics. Sensitivity analyses to assess the influence of individual studies on the pooled estimate. Publication bias was investigated using funnel plots and Egger’s regression test. Analyses were performed by using Review Manager 5.3 and Stata 11.0.

          Results

          Thirteen studies with a total of 4646 participants (2379 PD patients and 2267 controls) were included in this meta-analysis. The current results showed that the serum UA levels in PD patients were significantly lower compared to sex and age-matched healthy controls (SMD: -0.49, 95% CI: [-0.67, -0.30], Z = 5.20, P < 0.001) and these results showed no geographic regional (Asia: SMD = −0.65, 95% CI [−0.84, −0.46], Z = 6.75, p <0.001; Non-Asia: SMD = −0.25, 95% CI [−0.43, −0.07], Z = 2.70, p = 0.007) and sex differences (women: SMD = −0.53, 95% CI [−0.70, −0.35], z = 5.98, p <0.001; men: SMD = −0.66, 95% CI [−0.87, −0.44], z = 6.03, p <0.001). Serum UA levels in middle-late stage PD patients with higher H&Y scales were significantly lower than early stage PD patients with lower H&Y scales (SMD = 0.63, 95% CI [0.36,0.89], z = 4.64, p <0.001).

          Conclusions

          Our study showed that the serum UA levels are significantly lower in PD and the level is further decreased as the disease progresses. Thus it might be a potential biomarker to indicate the risk and progression of PD.

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          Most cited references34

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          Uric acid and oxidative stress.

          Uric acid is the final product of purine metabolism in humans. The final two reactions of its production catalyzing the conversion of hypoxanthine to xanthine and the latter to uric acid are catalysed by the enzyme xanthine oxidoreductase, which may attain two inter-convertible forms, namely xanthine dehydrogenase or xanthine oxidase. The latter uses molecular oxygen as electron acceptor and generates superoxide anion and other reactive oxygen products. The role of uric acid in conditions associated with oxidative stress is not entirely clear. Evidence mainly based on epidemiological studies suggests that increased serum levels of uric acid are a risk factor for cardiovascular disease where oxidative stress plays an important pathophysiological role. Also, allopurinol, a xanthine oxidoreductase inhibitor that lowers serum levels of uric acid exerts protective effects in situations associated with oxidative stress (e.g. ischaemia-reperfusion injury, cardiovascular disease). However, there is increasing experimental and clinical evidence showing that uric acid has an important role in vivo as an antioxidant. This review presents the current evidence regarding the antioxidant role of uric acid and suggests that it has an important role as an oxidative stress marker and a potential therapeutic role as an antioxidant. Further well designed clinical studies are needed to clarify the potential use of uric acid (or uric acid precursors) in diseases associated with oxidative stress.
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            Uric acid as a CNS antioxidant.

            Oxidative damage is a consistent finding in a number of central nervous system (CNS) disorders. Uric acid (UA) is a potent hydrophilic antioxidant that is modified by diet and drug. Several lines of evidence suggest that plasma UA may modulate outcomes in neurologic disease, but little attention has been paid to CNS levels of UA. Our objective was to test the hypothesis that cerebrospinal fluid (CSF) UA is determined by plasma UA, modified by blood-brain barrier (BBB) integrity and associated with rate of cognitive decline in Alzheimer's disease (AD). Also, since UA and ascorbic acid may act as antioxidants for one another, we also explored a potential interaction between them in the brain. Thirty-two patients with mild to moderate AD (Mini-Mental Status Exam 19 +/- 5) participated in a longitudinal biomarker study for one year involving standardized clinical assessments. CSF and blood were collected at baseline for UA, ascorbic acid, and albumin. Cognitive measures were collected at baseline and again one year later. CSF UA was independent of age, gender, and AD severity. CSF and plasma UA were positively correlated (r=0.669, p=0.001) and BBB impairment was associated with higher CSF levels of UA (p=0.028). Neither plasma nor CSF UA reached significant association with rates of cognitive decline over 1 year. CSF UA and CSF ascorbic acid were positively correlated (r=0.388, p=0.001). The hypothesis that CSF UA is determined by plasma UA and BBB integrity is supported, as is the hypothesis that UA and ascorbic acid are associated in CSF but not plasma. Adequately powered prospective studies would help assess any role for UA in primary and secondary prevention of AD.
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              Plasma urate and Parkinson's disease in the Atherosclerosis Risk in Communities (ARIC) study.

              Higher plasma urate concentration has been linked to lower risk of Parkinson's disease in men, but data are lacking on women and African Americans. The authors examined plasma urate in relation to Parkinson's disease in the biracial, population-based Atherosclerosis Risk in Communities (ARIC) cohort. Between 1987 and 1989, 15,792 participants, aged 45-64 years, were recruited from 4 US communities and have since been followed with 3 triennial visits and annual surveillance. Plasma urate was measured at visits 1 and 2, and the concentrations were highly correlated. From visit 1 through 2004, 95 potential cases of Parkinson's disease were identified from multiple sources. Odds ratios and 95% confidence intervals were calculated from multivariate logistic regression models. Plasma urate concentration was inversely associated with Parkinson's disease occurrence. The odds ratios between extreme quartiles of plasma urate were 0.4 (95% confidence interval: 0.2, 0.8) in the overall analysis, 0.3 (95% confidence interval: 0.1, 0.7) for men, and 0.4 (95% confidence interval: 0.2, 1.0) for Caucasians. Such an association was also suggested among women and African Americans but was not statistically significant because of small sample sizes. These data support the previous finding that urate may be a protective factor against Parkinson's disease.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                20 March 2017
                2017
                : 12
                : 3
                : e0173731
                Affiliations
                [1 ]Department of Anatomy, Guizhou Medical University, Guiyang, China
                [2 ]Department of Biology, Guizhou Medical University, Guiyang, China
                [3 ]Department of Neurology, BaiYun Hospital, Guizhou Medical University, Guiyang, China
                [4 ]Key Laboratory of Endemic and Ethnic Diseases, Ministry of Education, P. R. China; Key Laboratory of Medical Molecular Biology, Guizhou Medical University, Guizhou Province, Guiyang, P. R. China
                [5 ]Department of Neurology, Affiliated Hospital, Guizhou Medical University, Guiyang, China
                Leibniz-Institut fur Pflanzengenetik und Kulturpflanzenforschung Gatersleben, GERMANY
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                • Conceptualization: MW LJ WFY.

                • Formal analysis: MW BZ WFY.

                • Funding acquisition: BZ MW.

                • Investigation: YG YHC ZLM CLZ.

                • Project administration: MW LJ WFY.

                • Supervision: MW LJ WFY.

                • Writing – original draft: MW.

                • Writing – review & editing: WFY.

                Article
                PONE-D-16-35760
                10.1371/journal.pone.0173731
                5358777
                28319195
                58816b06-248f-432b-af15-4bdad254b7ac
                © 2017 Wen et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 8 September 2016
                : 24 February 2017
                Page count
                Figures: 5, Tables: 3, Pages: 13
                Funding
                Funded by: Natural Science Foundation of Guizhou Province of China
                Award ID: LG[2012]02
                Award Recipient :
                Funded by: Natural Science Foundation of Guizhou Province of China
                Award ID: LG[2011]023
                Award Recipient : wen min
                This study was supported by the Natural Science Foundation of Guizhou Province of China (LG [2012]021 and LG[2011]023).
                Categories
                Research Article
                Physical Sciences
                Chemistry
                Chemical Compounds
                Acids
                Uric Acid
                Medicine and Health Sciences
                Neurology
                Neurodegenerative Diseases
                Movement Disorders
                Parkinson Disease
                Research and Analysis Methods
                Mathematical and Statistical Techniques
                Statistical Methods
                Meta-Analysis
                Physical Sciences
                Mathematics
                Statistics (Mathematics)
                Statistical Methods
                Meta-Analysis
                Biology and Life Sciences
                Biochemistry
                Neurochemistry
                Neurochemicals
                Dopaminergics
                Biology and Life Sciences
                Neuroscience
                Neurochemistry
                Neurochemicals
                Dopaminergics
                Biology and Life Sciences
                Cell Biology
                Oxidative Stress
                Biology and Life Sciences
                Cell Biology
                Cellular Types
                Animal Cells
                Neurons
                Biology and Life Sciences
                Neuroscience
                Cellular Neuroscience
                Neurons
                Biology and Life Sciences
                Biochemistry
                Antioxidants
                Earth Sciences
                Geography
                Regional Geography
                Custom metadata
                All relevant data are within the paper and its Supporting Information files.

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