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The relationship between monoamine oxidase B (MAOB) A644G polymorphism and Parkinson disease risk: a meta-analysis.

ABSTRACT: Many studies were conducted to assess the relationship between Monoamine oxidase B (MAOB) A644G polymorphism and susceptibility to Parkinson disease (PD). However, the results were inconsistent and inconclusive.A meta-analysis was conducted from all published studies on the associations between monoamine oxidase B (MAOB) A644G polymorphism and Parkinson disease.In this present study, the possible relationship between MAOB A644G polymorphism and PD risk was assessed by a meta-analysis. Eligible articles were identified for the period up to March 2013. Pooled odds ratios (OR) with 95% confidence intervals (CI) were appropriately derived from fixed-effects models.Twenty case-control studies with a total of 2846 cases and 3508 controls were eligible. In a recessive model, MAOB A644G polymorphism was associated with PD risk (OR=1.32, 95% CI 1.18-1.47, P < .001). Subgroup analyses by ethnicity and gender also found significant relationships between this polymorphism and PD risk.This meta-analysis suggested that MAOB A644G polymorphism may be associated with PD development.

SUBMITTER: Liu Y

PROVIDER: S-EPMC6074924 | biostudies-literature | 2014 Jan-Feb

REPOSITORIES: biostudies-literature

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The relationship between monoamine oxidase B (MAOB) A644G polymorphism and Parkinson disease risk: a meta-analysis.

Liu Ying Y Wang Zhiyun Z Zhang Benshu B

Annals of Saudi medicine 20140101 1

<h4>Background and objectives</h4>Many studies were conducted to assess the relationship between Monoamine oxidase B (MAOB) A644G polymorphism and susceptibility to Parkinson disease (PD). However, the results were inconsistent and inconclusive.<h4>Design and settings</h4>A meta-analysis was conducted from all published studies on the associations between monoamine oxidase B (MAOB) A644G polymorphism and Parkinson disease.<h4>Methods</h4>In this present study, the possible relationship between M ...[more]

PMID: 24658549

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Project description:Parkinson disease (PD) is the second most common neurodegenerative disorder after Alzheimer disease, whereas Gaucher disease (GD) is the most frequent lysosomal storage disorder caused by homozygous mutations in the glucocerebrosidase (GBA1) gene. Increased risk of developing PD has been observed in both GD patients and carriers. It has been estimated that GBA1 mutations confer a 20- to 30-fold increased risk for the development of PD, and that at least 7-10% of PD patients have a GBA1 mutation. To date, mutations in the GBA1 gene constitute numerically the most important risk factor for PD. The type of PD associated with GBA1 mutations (PD-GBA1) is almost identical to idiopathic PD, except for a slightly younger age of onset and a tendency to more cognitive impairment. Importantly, the pathology of PD-GBA1 is identical to idiopathic PD, with nigral dopamine cell loss, Lewy bodies, and neurites containing alpha-synuclein. The mechanism by which GBA1 mutations increase the risk for PD is still unknown. However, given that clinical manifestation and pathological findings in PD-GBA1 patients are almost identical to those in idiopathic PD individuals, it is likely that, as in idiopathic PD, alpha-synuclein accumulation, mitochondrial dysfunction, autophagic impairment, oxidative and endoplasmic reticulum stress may contribute to the development and progression of PD-GBA1. Here, we review the GBA1 gene, its role in GD, and its link with PD. The impact of glucocerebrosidase 1 (GBA1) mutations on functioning of endoplasmic reticulum (ER), lysosomes, and mitochondria. GBA1 mutations resulting in production of misfolded glucocerebrosidase (GCase) significantly affect the ER functioning. Misfolded GCase trapped in the ER leads to both an increase in the ubiquitin-proteasome system (UPS) and the ER stress. The presence of ER stress triggers the unfolded protein response (UPR) and/or endoplasmic reticulum-associated degradation (ERAD). The prolonged activation of UPR and ERAD subsequently leads to increased apoptosis. The presence of misfolded GCase in the lysosomes together with a reduction in wild-type GCase levels lead to a retardation of alpha-synuclein degradation via chaperone-mediated autophagy (CMA), which subsequently results in alpha-synuclein accumulation and aggregation. Impaired lysosomal functioning also causes a decrease in the clearance of autophagosomes, and so their accumulation. GBA1 mutations perturb normal mitochondria functioning by increasing generation of free radical species (ROS) and decreasing adenosine triphosphate (ATP) production, oxygen consumption, and membrane potential. GBA1 mutations also lead to accumulation of dysfunctional and fragmented mitochondria. This article is part of a special issue on Parkinson disease.

Project description:BackgroundEpidemiological studies have evaluated the association between nicotinamide adenine dinucleotide phosphate (NADPH) oxidase p22(phox) C242T polymorphism and risk of ischemic cerebrovascular disease (ICVD), but the results remain inconclusive. This meta-analysis was therefore designed to clarify these controversies.Methodology/principal findingsSystematic searches of electronic databases Embase, PubMed and Web of Science, as well as hand searching of the references of identified articles and the meeting abstracts were performed. Statistical analyses were performed using software Review Manager (Version 5.1.7) and Stata (Version 11.0). The pooled odds ratios (ORs) with 95% confidence intervals (95%CIs) were performed. Fixed or random effects model was separately used depending on the heterogeneity between studies. Publication bias was tested by Begg's funnel plot and Egger's regression test. A total of 6 studies including 1,948 cases and 2,357 controls were combined showing no statistical evidence of association between NADPH oxidase p22(phox) C242T polymorphism and overall ICVD (allelic model: OR?=?1.08, 95%CI?=?0.93-1.26; additive model: OR?=?1.33, 95%CI?=?0.81-2.17; dominant model: OR?=?1.00, 95%CI?=?0.86-1.15; recessive model: OR?=?1.06, 95%CI?=?0.77-1.45). Significant association was found in large-artery atherosclerotic stroke subgroup (allelic model: OR?=?1.12, 95%CI?=?0.88-1.41; additive model: OR?=?1.36, 95%CI?=?0.60-3.09; dominant model: OR?=?1.25, 95%CI?=?0.74-2.11; recessive model: OR?=?2.17, 95%CI?=?1.11-4.23). No statistical evidence of significant association was observed for small-vessel occlusive stroke, as well as Asian subgroup and Caucasian subgroup. Statistical powers on the combined sample size (total and subgroup) were all lower than 80%.Conclusions/significanceThis meta-analysis indicates that NADPH oxidase p22(phox) C242T polymorphism is more associated with large-artery atherosclerotic stroke than small-vessel occlusive stroke. However, this conclusion should be interpreted with caution due to the small sample size. Larger sample-size studies with homogeneous ICVD patients and well-matched controls are required.

Dataset Information

The relationship between monoamine oxidase B (MAOB) A644G polymorphism and Parkinson disease risk: a meta-analysis.

Publications

The relationship between monoamine oxidase B (MAOB) A644G polymorphism and Parkinson disease risk: a meta-analysis.

Similar Datasets

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