NR4A2 genetic variation and Parkinson's disease: Evidence from a systematic review and meta-analysis

Li, Hongmei; Liu, Hongbo; Li, Ting; Cui, Jiayi; Fu, Yingmei; Ren, Jun; Sun, Xiujia; Jiang, Ping; Yu, Shunying; Li, Chunbo

doi:10.1016/j.neulet.2017.01.062

Cited by 16 publications

(16 citation statements)

References 58 publications

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“…In addition, the rs34884856 promoter variant has been associated with alcohol dependence in people with Mexican ancestry [36]. It should be highlighted that the genotypic frequencies observed in our study are similar to those identi ed in Asian populations and different from those reported for Caucasian populations in diseases associated with dopamine dysfunction such as schizophrenia [29,33,34].…”

Section: Genetic Association Study Between Nr4a2 Variants and Schizopsupporting

confidence: 63%

“…For association analysis between genotypes, gene expression and working memory, we used the recessive model considering the minor frequency allele and the risk allele described in various studies [32,33,34,35,36]. The recessive model postulates that the risk of the disease occurs in the homozygotes for risk allele.…”

Section: Discussionmentioning

confidence: 99%

“…The two genetic variants analyzed in the present study have been associated with other neurological, psychiatric disorders, and addiction, which are also related with dysfunction of the dopaminergic system. In particular, the rs35479735 intronic 6 variant has been associated with Parkinson's disease in Asian, Caucasian, and Mexican populations [33][34][35]. In addition, the rs34884856 promoter variant has been associated with alcohol dependence in people with Mexican ancestry [36].…”

Section: Introductionmentioning

confidence: 99%

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Working Memory Deficits in Schizophrenia Are Associated With the Rs34884856 Variant and Expression Levels of the NR4A2 Gene in a Sample Mexican Population: A Case Control Study

Ruiz-Sánchez

Jiménez-Genchi

Alcántara-Flores

et al. 2020

Preprint

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Background Cognitive functions represent useful endophenotypes to identify the association between genetic variants and schizophrenia. In this sense, the NR4A2 gene has been implicated in schizophrenia and cognition in different animal models and clinical trials. We hypothesized that the NR4A2 gene is associated with working memory performance in schizophrenia. This study aimed to analyze two variants and the expression levels of the NR4A2 gene with susceptibility to schizophrenia, as well as to evaluate whether possession of NR4A2 variants influence the possible correlation between gene expression and working memory performance in schizophrenia. Methods The current study included 187 schizophrenia patients and 227 controls genotyped for two of the most studied NR4A2 genetic variants in neurological and neuropsychiatric diseases. Genotyping was performed using High Resolution Melt and sequencing techniques. In addition, mRNA expression of NR4A2 was performed in peripheral mononuclear cells of 112 patients and 118 controls. A group of these participants, 54 patients and 87 controls, performed the working memory index of the WAIS III test. Results Both genotypic frequencies of the two variants and expression levels of the NR4A2 gene showed no significant difference when in patients versus controls. However, patients homozygous for the rs34884856 promoter variant showed a positive correlation between expression levels and auditory working memory. In these patients, a decrease of NR4A2 mRNA expression was related to working memory impairment. Conclusions Our finding suggested that changes in expression levels of the NR4A2 gene could be associated with working memory in schizophrenia depending on patients´ genotype in a sample from a Mexican population.

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Section: Genetic Association Study Between Nr4a2 Variants and Schizopsupporting

confidence: 63%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Working Memory Deficits in Schizophrenia Are Associated With the Rs34884856 Variant and Expression Levels of the NR4A2 Gene in a Sample Mexican Population: A Case Control Study

Ruiz-Sánchez

Jiménez-Genchi

Alcántara-Flores

et al. 2020

Preprint

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“…As known, Nurr1 plays an important role in the maturation of mDA neurons (Kadkhodaei et al, 2009), linking its deficiency mainly to PD. In fact, several human mutations in the gene encoding for Nurr1 protein, the NR4A2 gene, are associated with late-onset familial PD (Le et al, 2003), and the SNPsrs35479735 (insertion/deletion of a G) seems to be a significant risk factor for the development of PD (Liu et al, 2017;Ruiz-Sánchez et al, 2017). Furthermore, Nurr1 gene expression level is down-regulated in blood of PD patients with progressive loss of DA neurons (Le et al, 2008;Liu et al, 2012;Montarolo et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

The transcription factor Nurr1 is up-regulated in amyotrophic lateral sclerosis patients and SOD1-G93A mice

Valsecchi

Boido

Montarolo

et al. 2020

Disease Models &Amp; Mechanisms

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Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that affects both lower and upper motor neurons (MNs) in the central nervous system (CNS). ALS etiology is highly multifactorial and multifarious, and an effective treatment is still lacking. Neuroinflammation is a hallmark of ALS and could be targeted to develop new therapeutic approaches. Interestingly, the transcription factor Nurr1 has been demonstrated to play an important role in inflammatory process in several neurological disorders, such as Parkinson's disease (PD) and Multiple Sclerosis (MS). In the present paper, we demonstrated for the first time that Nurr1 expression levels were up-regulated in the peripheral blood of ALS patients. Moreover, we investigated Nurr1 function in the SOD1-G93A mouse model of ALS. Interestingly, Nurr1 was strongly upregulated in the spinal cord during the asymptomatic and early symptomatic phases of the disease, where it promoted the up-regulation of the BDNF mRNA and the repression of NF-kB pro-inflammatory targets, such as iNOS. Therefore, we hypothesize that Nurr1 is activated in an early phase of the disease as survival endogenous anti-inflammatory mechanism, although not sufficient to revert disease progression. Based on these observations, Nurr1 could represent a potential biomarker for ALS and a promising target for future therapies for ASL.

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“…Moreover, we found our identified genes in figure 5 had been shown in other studies to be associated with disease progression in NDGDs. Specifically, Liu H et al has shown a link between NR4A2 and PD [49]; Taguchi K et al found POU2F1 to be linked to AD incidence [50]; A Hggmark et al found SLC9A3R1 and SLC39A11 are associated with AD [51]; J Wang et al found SCN1A and FOS is associated with ED [52]; J Wang et al showed SCN1A and FOS to be linked to ED [52]; and Mahurkar et al showed GPC5 to be linked to MSD [53]. In summary, we have found that the welding fume associated genes have strong associations with progression of PD, AD, LGD, ED and MSD and these findings are supported by previous work on these neurodegenerative diseases by other researchers.…”

Section: Discussionmentioning

confidence: 99%

Genetic effects of welding fumes on the progression of neurodegenerative diseases

et al. 2019

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Background: Welding involves exposure to fumes, gases and radiant energy that can be hazardous to human health. Welding fumes (WFs) comprise a complex mixture of metallic oxides, silicates and fluorides that may result in different health effects. Inhalation of WFs in large quantities over a long periods may pose a risk of developing neurodegenerative diseases (NDGDs), but the nature of this risk is poorly understood. To address this we performed transcriptomic analysis to identify links between WF exposure and NDGDs. Methods: We developed quantitative frameworks to identify the gene expression relationships of WF exposure and NDGDs. We analyzed gene expression microarray data from fume-exposed tissues and NDGDs including Parkinson's disease (PD), Alzheimer's disease (AD), Lou Gehrig's disease (LGD), Epilepsy disease (ED) and multiple sclerosis disease (MSD) datasets. We constructed disease-gene relationship networks and identified dysregulated pathways, ontological pathways and protein-protein interaction sub-network using multilayer network topology and neighborhood-based benchmarking. Results: We observed that WF associated genes share 18, 16, 13, 19 and 19 differentially expressed genes with PD, AD, LGD, ED and MSD respectively. Gene expression dysregulation along with relationship networks, pathways and ontologic analysis indicate that WFs may be linked to the progression of these NDGDs. Conclusions: Our developed network-based approach to analysis and investigate the genetic effects of welding fumes on PD, AD, LGD, ED and MSD neurodegenerative diseases could be helpful to understand the causal influences of WF exposure for the progression of the NDGDs.

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NR4A2 genetic variation and Parkinson's disease: Evidence from a systematic review and meta-analysis

Cited by 16 publications

References 58 publications

Working Memory Deficits in Schizophrenia Are Associated With the Rs34884856 Variant and Expression Levels of the NR4A2 Gene in a Sample Mexican Population: A Case Control Study

Working Memory Deficits in Schizophrenia Are Associated With the Rs34884856 Variant and Expression Levels of the NR4A2 Gene in a Sample Mexican Population: A Case Control Study

The transcription factor Nurr1 is up-regulated in amyotrophic lateral sclerosis patients and SOD1-G93A mice

Genetic effects of welding fumes on the progression of neurodegenerative diseases

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