Meta-analysis of association between PITX3 gene polymorphism and Parkinson's disease

Tang, Lanhua; Zhao, Shushan; Wang, Meiping; Sheth, Aniruddha; Zhao, Zijin; Chen, Luyao; Fan, Xue‐Gong

doi:10.1016/j.jns.2012.02.025

Cited by 14 publications

(6 citation statements)

References 35 publications

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“…In contrast with the results of another previous meta-analysis reported by Tang et al [29], which did not include data from the studies of Cai et al [16] and Gui et al [15], we did not find an association between rs4919621 SNP and PD risk in the Caucasian population. The increased risk for early-onset PD related with rs2281983 and rs4919621 SNPs found in that study was also found in the present meta-analyses in Caucasian subjects, as was previously commented on but not confirmed after including data from Cai et al [16].…”

Section: Discussioncontrasting

confidence: 99%

PITX3 and Risk for Parkinson's Disease: A Systematic Review and Meta-Analysis

et al. 2013

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Background/Aims: Several single nucleotide polymorphisms (SNPs) in the PITX3 gene have been associated with the risk for Parkinson's disease (PD). We conducted a systematic review and a meta-analysis including all the studies published on the risk of PD related with these polymorphisms. Methods: The systematic review was done using several databases. Eligible studies were included in the meta-analysis that was carried out using Meta-DiSc 1.1.1 software. Heterogeneity between studies was tested using the Q-statistic. Results: The meta-analysis included eight association studies for the PITX3 rs3758549 SNP (4,052 PD patients, 3,949 controls), eight studies for the PITX3 rs2281983 SNP (4,309 PD patients, 4,287 controls), and six studies for the rs4919621 SNP (2,724 PD patients, 2,285 controls), and the risk for PD, global diagnostic odds ratios (95% confidence intervals) for rs3758549, rs2281983, and rs4919621 were, respectively, 1.00 (0.89-1.12) (p = 0.979), 0.99 (0.91-1.09) (p = 0.896), and 0.98 (0.83-1.16) (p = 0.844) for the total group. The separate analysis in Caucasian and Chinese subjects on the frequency of the minor allele of the three SNPs analyzed did not show significant differences between PD patients and controls in both subgroups. rs2281983 and rs4919621 SNPs were related with early-onset PD risk in Caucasians. Conclusion: The results of the meta-analysis suggest that rs3758549, rs2281983, and rs4919621 SNPs are not major determinants of the risk for PD.

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Section: Discussioncontrasting

confidence: 99%

PITX3 and Risk for Parkinson's Disease: A Systematic Review and Meta-Analysis

et al. 2013

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“…Mutations in PITX3 have been implicated in anterior segmental mesenchymal dysgenesis and congenital cataract [Burdon et al, ; Summers et al, ]. PITX3 polymorphism has also been associated with Parkinson disease [Tang et al, ]. There were no reports of Parkinsonian features in our cohort, though children may not be expected to show these.…”

Section: Discussionmentioning

confidence: 61%

FOXP1 mutations cause intellectual disability and a recognizable phenotype

Fevre

Taylor²,

Malek³

et al. 2013

American J of Med Genetics Pt A

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Mutations in FOXP1, located at 3p13, have been reported in patients with global developmental delay (GDD), intellectual disability (ID), and speech defects. Mutations in FOXP2, located at 7q31, are well known to cause developmental speech and language disorders, particularly developmental verbal dyspraxia (DVD). FOXP2 has been shown to work co-operatively with FOXP1 in mouse development. An overlap in FOXP1 and FOXP2 expression, both in the songbird and human fetal brain, has suggested that FOXP1 may also have a role in speech and language disorders. We report on a male child with a 0.19 MB intragenic deletion that is predicted to result in haploinsufficiency of FOXP1. Review of our patient and others reported in the literature reveals an emerging phenotype of GDD/ID with moderate to severe speech delay where expressive speech is most severely affected. DVD appears not to be a distinct feature in this group. Facial features include a broad forehead, downslanting palpebral fissures, a short nose with broad tip, relative or true macrocephaly, a frontal hair upsweep and prominent digit pads. Autistic traits and other behavioral problems are likely to be associated with haploinsufficiency of FOXP1. Congenital malformations may be associated.

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“…Several developmental transcription factors, including Nurr1, Lmx1a/b, Engrailed 1, and Pitx3, remain expressed in mature DA neurons, and nucleotide polymorphisms in human genes encoding these factors have been associated with PD (11)(12)(13)(23)(24)(25)(26). Moreover, analysis of postmortem brain tissue has demonstrated down-regulation of Nurr1 and other key transcription factors in remaining DA neurons in PD, and significantly reduced Nurr1 and Pitx3 mRNA expression levels in peripheral blood cells in PD patients (14,15).…”

Section: Discussionmentioning

confidence: 99%

Transcription factor Nurr1 maintains fiber integrity and nuclear-encoded mitochondrial gene expression in dopamine neurons

Kadkhodaei

Alvarsson

Schintu

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

153

182

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Developmental transcription factors important in early neuron specification and differentiation often remain expressed in the adult brain. However, how these transcription factors function to mantain appropriate neuronal identities in adult neurons and how transcription factor dysregulation may contribute to disease remain largely unknown. The transcription factor Nurr1 has been associated with Parkinson's disease and is essential for the development of ventral midbrain dopamine (DA) neurons. We used conditional Nurr1 genetargeted mice in which Nurr1 is ablated selectively in mature DA neurons by treatment with tamoxifen. We show that Nurr1 ablation results in a progressive pathology associated with reduced striatal DA, impaired motor behaviors, and dystrophic axons and dendrites. We used laser-microdissected DA neurons for RNA extraction and next-generation mRNA sequencing to identify Nurr1-regulated genes. This analysis revealed that Nurr1 functions mainly in transcriptional activation to regulate a battery of genes expressed in DA neurons. Importantly, nuclear-encoded mitochondrial genes were identified as the major functional category of Nurr1-regulated target genes. These studies indicate that Nurr1 has a key function in sustaining high respiratory function in these cells, and that Nurr1 ablation in mice recapitulates early features of Parkinson's disease. NR4A2 | nuclear receptor | laser capture microdissection | RNA sequencing | orphan receptor U nder experimental conditions, somatic differentiated cells can undergo reprogramming into other cell types or induced pluripotent stem cells (1). This remarkable plasticity raises questions of how the differentiated cellular identity is maintained for extended periods in normal life (2). Of particular relevance is how neurons, which should retain their specific functions for decades in a human brain, stably maintain their unique differentiated properties, and how disrupted maintenance of the correct differentiated identity may be related to disease. Under embryonic development, signaling events induce the expression of transcription factors that combinatorially function to specify appropriate identities and differentiation of specific neuron types. Many of these transcription factors continue to be expressed in adult neurons as well; however, little is known of their functions in the adult brain, or the extent to which they contribute to the stability of the differentiated state (3).Degeneration of ventral midbrain (VMB) dopamine (DA) neurons, particularly neurons of the substantia nigra compacta (SNc), causes many of the characteristic symptoms in patients with Parkinson's disease (PD). PD is characterized by a progressive pathology involving the appearance of insoluble protein inclusions known as Lewy bodies and eventually the death of neurons. Several studies have indicated that loss of striatal DA and other dopaminergic properties cause symptoms in PD long before cell bodies within the SNc actually die (4). Thus, PD cell pathology may influence differentiated...

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Meta-analysis of association between PITX3 gene polymorphism and Parkinson's disease

Cited by 14 publications

References 35 publications

<b><i>PITX3</i></b> and Risk for Parkinson's Disease: A Systematic Review and Meta-Analysis

<b><i>PITX3</i></b> and Risk for Parkinson's Disease: A Systematic Review and Meta-Analysis

FOXP1 mutations cause intellectual disability and a recognizable phenotype

Transcription factor Nurr1 maintains fiber integrity and nuclear-encoded mitochondrial gene expression in dopamine neurons

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