Low uric acid levels in patients with Parkinson's disease: evidence from meta-analysis.
ABSTRACT: The association between Parkinson's disease (PD) and uric acid levels has gained intensive interest in recent years. We applied meta-analysis to investigate serum uric acid levels in patients with PD in comparison with healthy controls.We searched three electronic databases and reference lists up to January 2013. Two collaborators reviewed all the articles and data disagreement was resolved through discussion. Six studies met the eligibility criteria and were included in the meta-analysis of uric acid levels in patients with PD in comparison with controls.1217 patients with PD and 1276 matched healthy controls.The meta-analysis results showed that patients with PD had lower levels of uric acid than healthy controls (summary standardised mean difference (SMD)=-0.52, 95% CI (-0.72 to -0.31)). Further gender subgroup analysis (summary SMD=-0.56, 95% CI (-0.72 to -0.41) for women; summary SMD=-0.62, 95% CI (-0.94 to -0.31) for men) indicated lower uric acid levels in patients with PD than healthy controls in women and men.It was found that patients with PD had lower serum levels of uric acid than healthy controls and this association was more significant in men than in women. More efforts are encouraged to explore the prognostic and therapeutic implications for PD of the present findings.
Project description: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.The aim of the present study was to clarify the potential relationship of uric acid with PD.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 I2 and H2 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.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).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.
Project description:<h4>Background</h4>Serum uric acid (UA) could exert neuro-protective effects against Alzheimer's disease (AD) via its antioxidant capacities. Many studies investigated serum UA levels in AD patients, but to date, results from these observational studies are conflicting.<h4>Methods</h4>We conducted a meta-analysis to compare serum UA levels between AD patients and healthy controls by the random-effects model. Studies were identified by searching PubMed, ISI Web of Science, EMBASE, and the Cochrane library databases from 1966 through July 2013 using the Medical Subject Headings and keywords without restriction in languages. Only case-control studies were included if they had data on serum UA levels in AD patients and healthy controls. Begg's funnel plot and Egger's regression test were applied to assess the potential publication bias. Sensitivity analyses and meta-regression were conducted to explore possible explanations for heterogeneity.<h4>Results</h4>A total of 11 studies met the inclusion criteria including 2708 participants were abstracted. Serum UA levels were not significantly different in AD patients compared to healthy controls (standardized mean difference (SMD)?=?-0.50; 95% confidence interval (CI): -1.23 to 0.22). Little evidence of publication bias was observed. Sensitivity analyses showed that the combined SMD was consistent every time omitting any one study, except only one study which greatly influenced the overall results. Meta-regression showed that year of publication, race, sample size, and mean age were not significant sources of heterogeneity.<h4>Conclusion</h4>Our meta-analysis of case-control studies suggests that serum UA levels do not differ significantly in AD patients, but there may be a trend toward decreased UA in AD after an appropriate interpretation. More well-designed investigations are needed to demonstrate the potential change of serum UA levels in AD patients.
Project description:Oxidative stress has been suggested to play a key role in Parkinson's disease, but inconsistent results were found in clinical studies. This study sought to quantitatively summarize the blood and cerebrospinal fluid (CSF) oxidative stress marker data in PD patients. We performed a systematic search of PubMed and Web of Science, and studies were included if they provided data on peripheral blood and CSF oxidative stress marker concentrations in PD patients and healthy control (HC) subjects. Data were extracted by three independent investigators from 80 included studies encompassing 7,212 PD patients and 6,037 HC subjects. Of the 22 oxidative stress markers analyzed, random effects meta-analysis showed that blood concentrations of 8-OhdG, MDA, nitrite, and ferritin were increased in patients with PD compared with HC subjects. In contrast, we showed that blood levels of catalase, uric acid, glutathione, and total-cholesterol were significantly down-regulated in patients with PD when compared with controls. There were no significant differences between PD patients and HC subjects for blood, Mn, Cu, Zn, Fe, SOD, albumin, glutathione peroxidase, vitamin E, ceruloplasmin, triglycerides, lactoferrin, transferrin, LDL-cholesterol, and HDL-cholesterol. Due to the limited number of CSF studies with small sample size, this meta-analysis only showed non-significant association between CSF 8-OhdG and PD. The findings of our meta-analysis demonstrated higher blood concentrations of 8-OhdG, MDA, nitrite and ferritin, and lower blood concentrations of catalase, uric acid, glutathione and total-cholesterol in PD patients, strengthening the clinical evidence that PD is accompanied by increased oxidative stress.
Project description:Individuals with Parkinson's disease (PD) have lower uric acid levels than those without PD, and the CC genotype and C minor allele of a single nucleotide polymorphism (SNP), rs1014290 of SLC2A9, are associated with lower uric acid levels. We investigated the association of rs1014290 with uric acid metabolism in a cohort of PD cases (220) and controls (110) in a Han Chinese population. Uric acid levels were determined and rs1014290 was assayed using a mutation-sensitive on/off switch technology. PD uric acid levels (291.65 ± 76.29??mol/L) were significantly lower than the controls (325.73 ± 74.23??mol/L, P < 0.001, t-test). Individuals with rs1014290 TT and CT genotypes had higher uric acid levels, and those with the CC genotype had the lowest uric acid levels among both control and PD cases. The CC genotype and the C minor allele were statistically more frequent in the PD group compared to the control group. Those with the CC genotype had a statistically significant higher risk of PD than those with the TT or TC genotype (odds ratio [OR] = 2.249, 95% confidence interval [CI]: 1.129-4.480, and P = 0.021). Thus, SLC2A9 rs1014290 is related to lower uric acid levels in PD patients and can be a risk factor for PD in the Han population.
Project description:OBJECTIVE:Insulin-like growth factor-1 (IGF-1) is reported to be neuroprotective in the setting of Parkinson's disease (PD), and there is increasing interest in the possible association of serum IGF-1 levels with PD patients, but with conflicting results. Therefore, we conducted a meta-analysis to evaluate the association of serum IGF-1 levels in de novo, drug naïve PD patients compared with healthy controls. METHODS:Pubmed, ISI Web of Science, OVID, EMBASE, and Cochrane library databases from 1966 to October 2014 were utilized to identify candidate studies using Medical Subjective Headings without language restriction. A random-effects model was chosen, with subgroup analysis and sensitivity analysis conducted to reveal underlying heterogeneity among the included studies. RESULTS:In this meta-analysis, we found that PD patients had higher serum IGF-1 levels compared with healthy controls (summary mean difference [MD] = 17.75, 95%CI = 6.01, 29.48). Subgroup analysis demonstrated that the source of heterogeneity was population differences within the total group. Sensitivity analysis showed that the combined MD was consistent at any time omitting any one study. CONCLUSIONS:The results of this meta-analysis demonstrate that serum IGF-1 levels were significantly higher in de novo, drug-naïve PD patients compared with healthy controls. Nevertheless, additional endeavors are required to further explore the association between serum IGF-1 levels and diagnosis, prognosis and early therapy for PD.
Project description:Background. Interleukin-6 (IL-6) is an important pro-inflammatory cytokine and has been implicated to play a role in the systemic inflammation of patients with chronic obstructive pulmonary disease (COPD). We conducted this meta-analysis to assess the association between serum IL-6 concentrations and COPD. Methods. PubMed and Embase were searched for eligible studies. Data were extracted by two investigators (Wei J, Xiong XF) independently and analyzed using Review Manager 5.3 and STATA 12.0 software. Standard mean differences (SMDs) and 95% confidence intervals (CI) were calculated. Results. Thirty-three studies were included in this meta-analysis. The serum IL-6 concentrations were higher in patients with stable COPD than healthy controls (SMD = 0.65, 95% CI [0.51-0.79]). COPD patients without major comorbidities also showed higher IL-6 levels than healthy controls (SMD = 0.74, 95% CI [0.56-0.91]). COPD patients with an forced expiratory volume in one second (FEV1) of either <50% predicted or >50% predicted had increased IL-6 concentrations compared to healthy controls (SMD = 0.77, 95% CI [0.48-1.05], SMD = 1.01, 95% CI [0.43-1.59], respectively). The serum IL-6 concentrations between mild-moderate and severe-very severe COPD patient groups were not found to be significant (SMD = -0.1, 95% CI [-0.65-0.44]). Conclusions. This meta-analysis indicated that patients with stable COPD had higher serum IL-6 concentrations than healthy controls. No evidence showing positive or negative association between IL-6 concentrations and the severity of pulmonary function impairment was found. The correlation between IL-6 levels and pulmonary function was weak in different severities of stable COPD patients.
Project description:<h4>Background</h4>The aim of our meta-analysis is to understand the relationship between the pathogenesis of osteoarthritis and the expression levels of vascular endothelial growth factor (VEGF) in multiple disease tissues in osteoarthritis patients.<h4>Methods</h4>The following electronic databases were searched, without language restrictions, to retrieve published studies relevant to VEGF and osteoarthritis: MEDLINE (1966?~?2013), the Cochrane Library Database (Issue 12, 2013), EMBASE (1980?~?2013), CINAHL (1982?~?2013), Web of Science (1945?~?2013) and the Chinese Biomedical Database (CBM) (1982?~?2013). Meta-analysis of the extracted data was performed using the STATA statistical software. Standardized mean difference (SMD) with its corresponding 95% confidence interval (95% CI) was calculated.<h4>Results</h4>A total of 11 case-control studies, containing 302 osteoarthritis patients and 195 healthy controls, met our selection criteria for this meta-analysis. Our analyses of the data available from multiple disease tissues demonstrate that VEGF expression levels in osteoarthritis patients are significantly higher than healthy controls (SMD?=?1.18, 95% CI: 4.91?~?9.11, P?<?0.001). A subgroup analysis based on ethnicity revealed that both Asian and Caucasian osteoarthritis patients had higher levels of VEGF expression compared to their respective healthy counterparts (Asians: SMD?=?5.49, 95% CI: 3.44?~?7.54, P?<?0.001; Caucasians: SMD?=?15.17, 95% CI: 5.21?~?25.13, P?=?0.003; respectively). We also performed other subgroup analyses based on country, language and sample source, and the results showed that, in all these subgroups, osteoarthritis patients had higher levels of VEGF expression than healthy controls (all P?>?0.05).<h4>Conclusion</h4>Our meta-analysis provides evidence that higher VEGF expression levels strongly correlate with the pathogenesis of osteoarthritis.
Project description:Introduction:The soluble urokinase-type plasminogen activator receptor (suPAR) has been found to be elevated in primary focal segmental glomerulosclerosis (pFSGS). However, its usefulness as a biomarker for FSGS remains controversial. We conducted a meta-analysis aiming at investigating the significance of suPAR in diagnosing pFSGS. Methods:Electronic databases (PubMed and EMBASE) were searched to identify studies comparing suPAR levels in FSGS patients and controls, from the earliest available date to May 1, 2018. A random-effects model with standardized mean difference (SMD) was used for meta-analyses. Risk of bias was assessed using the Newcastle-Ottawa quality assessment scale. Results:A total of 187 articles were screened, and the final analysis included 13 articles. In comparison to healthy controls, serum suPAR levels were significantly increased in pFSGS patients (SMD, 1.07, 95% confidence interval (CI) 0.65 to 1.48; participants = 814; studies = 9, I 2 = 85%). Higher suPAR levels were also found in patients with pFSGS compared to those with minimal change disease (SMD 0.53, 95% CI 0.22 to 0.84). Of note, such a difference was not found in pediatric groups (SMD 0.42, 95% CI -0.13 to 0.96) while it was more evidently noted in adult patients (SMD 1.32, 95% CI 0.90 to 1.74). Serum suPAR levels did not differ between pFSGS patients in remission compared to those in active proteinuric state (SMD 0.29, 95% CI -0.30 to 0.88). Comparison with membranous nephropathy and IgA nephropathy showed no significant difference. Conclusions:Our meta-analysis demonstrated that, in comparison to both healthy controls and controls with minimal change disease, suPAR levels were significantly higher in adult patients with pFSGS. suPAR levels did not differ between pFSGS patients during the initial period of diagnosis and those in remission.
Project description:The objective of the study is to assess the TNF-? levels in PCOS patients and healthy controls. A comprehensive electronic search in Medline, Embase, and the Cochrane Library database was conducted up to July 2016. Random-effects model was used to estimate the standardized mean differences (SMDs) with 95% confidence intervals (CIs). Twenty-nine studies with a total of 1960 participants (1046 PCOS patients and 914 controls) were included in this meta-analysis. The TNF-? levels in PCOS patients were significantly higher than those in controls (random-effects, SMD = 0.60, 95% CI = 0.28-0.92, P<0.001). With regard to the subgroup analyses stratified by ethnicity, study quality, methods, and BMI, significantly high TNF-? levels were found in patients with PCOS in almost all of these subgroups. In the subgroup stratified by HOMA-IR ratio and T ratio, significant differences were only observed in the subgroups with HOMA-IR ratio of >1.72(SMD = 0.967, 95% CI = 0.103-1.831, P = 0.028, I2 = 93.5%) and T ratio>2.10 (SMD = 1.420, 95% CI = 0.429-2.411, P = 0.005, I2 = 96.1%). By meta-regression it was suggested that ethnicity might contribute little to the heterogeneity between the included studies. Through cumulative meta-analysis and sensitivity analysis it was supposed that the higher TNF-? levels of PCOS patients compared to healthy controls was stable and reliable. This meta-analysis suggests that the circulating TNF-? levels in women with PCOS are significantly higher than those in healthy controls. It may be involved in promoting insulin resistance and androgen excess of PCOS.
Project description:Intracerebral hemorrhage (ICH) has the highest mortality rate in all strokes. However, controversy still exists concerning the association between plasma homocysteine (Hcy) and ICH. A systematic review and meta-analysis was conducted using Pubmed, Embase, and Web of Science up to April 18, 2017. Standard mean difference (SMD) for mean differences of plasma Hcy levels with 95% confidence intervals (CI) was calculated. Seven studies including 667 ICH patients and 1821 ischemic stroke patients were identified for meta-analysis. Our results showed that Hcy levels in ICH patients were significantly higher than those in healthy controls (SMD?=?0.59, 95% CI?=?0.51-0.68, P?<?0.001); no statistic differences were found in the comparisons of Hcy levels between ICH and ischemic stroke (SMD?=?-0.03, 95% CI?=?-0.13-0.06, P?>?0.05); further subgroup analysis of ethnicity (Asians: SMD?=?0.57, 95% CI?=?0.48-0.66, P?<?0.001; Caucasians: SMD?=?0.77, 95% CI?=?0.51-1.02, P?<?0.001) and sample size (small samples: SMD?=?0.55, 95% CI?=?0.30-0.80, P?<?0.001; large samples size: SMD?=?0.60, 95% CI?=?0.51-0.69, P?<?0.001) in relation to Hcy levels between ICH and healthy controls did not change these results. In conclusion, Hcy level may be an aggravating factor in atherosclerosis, which is positively associated with high risk of ICH. Race-specific differences between Asians and Caucasians have no impact on the risk of ICH.