Meta-analysis of association between PITX3 gene polymorphism and Parkinson's disease
Introduction
Parkinson's disease (PD), a neurodegenerative disorder clinically characterized by bradykinesia, rigidity, resting tremor, postural instability, and a variety of other motor and nonmotor symptoms [1], has been receiving growing attention as a chronic condition of old age. At the age of 65 approximately 1% of the population is affected, increasing to 4–5% at the age of 85 [2].
Despite substantial research, the etiology of PD still remains unclear. It has been recognized that PD is caused by multiple factors such as genetic, environmental and others [3]. These factors lead to oxidative stress, mitochondrial dysfunction and inflammation which results in nigral dopaminergic (DAergic) neuron degeneration [3], [4], [5]. The loss of the DAergic neurons in the substantia nigra pars compacta (SNpc), the major pathological hallmark of PD, results in dysfunctioning of the nigrostriatal DA system. Clinically, the first motor symptoms of PD are observable when 60–80% of the DAergic neurons are lost [6].
PITX3 (paired-like homeodomain transcription factor 3) belonging to a pituitary homeobox subfamily, and being a homeodomain-containing transcription factor [7], is essential to the differentiation and maintenance of DA neurons in midbrain during development [8], [9]. From this, we can hypothesize that a polymorphism in the PITX3 region can lead to the loss of DAergic neurons resulting in PD. Several studies have investigated the association between a single nucleotide polymorphism in PITX3 gene and the manifestation of PD [10], [11], [12], [13], [14], [15], [16], [17], however their results were controversial. To derive a more precise estimation about whether a polymorphism within the PITX3 gene confers a greater risk of the development of PD, we have therefore conducted this meta-analysis based on previous reports.
Section snippets
Literature search
To identify eligible studies for this meta-analysis, we searched the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, and Science Citation Index EXPANDED in all languages which were published up to May 2011. The search strategy was based on Boolean combinations of the keywords ((PITX3 or Pitx3 or PiTX3 or Plx3 or pituitary homeobox 3 or paired-like homeodomain transcription factor 3) AND (Parkinson's disease or Parkinson's disease or Parkinson's
Results of the search
A total of 176 potentially useful individual articles by the initial search (Fig. 1) were identified. After review of the titles by two independent review authors (LT, SZ), 142 studies were excluded as being irrelevant to PITX3 (n = 77), review articles (n = 30) or index and contents (n = 35). Following this, 24 studies were excluded after the abstract review, nine of them were not human studies, and 15 of them were not relevant to polymorphisms. Finally 10 articles were retrieved for further
Discussion
In the adult central nervous system, approximately 75% of the DA neurons are located in the midbrain, including the SNpc and ventral tegmental area (VTA). And of the three main pathways in the midbrain DAergic systems, the mesostriatal pathway plays an important role in the control of voluntary associated movements [22]. If this pathway dysfunctions, it will likely cause SNpc DA neuronal loss allowing a DA concentration decrease in the dorsal striatum which finally lead to movement disorder in
Conflict of interest
The authors do not have any conflict of interest.
Acknowledgments
The authors would like to thank the anonymous reviewers for their valuable comments and suggestions to improve the quality of the paper.
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