No association of GPNMB rs156429 polymorphism with Parkinson’s disease, amyotrophic lateral sclerosis and multiple system atrophy in Chinese population

Xu, Yaqian; Chen, Yongping; Ou, Ruwei; Wei, Qianqian; Cao, Bei; Chen, Ke; Shang, Huifang

doi:10.1016/j.neulet.2016.04.060

Cited by 14 publications

(12 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Interestingly, a two-stage genome-wide association (GWA) meta-analysis associated GPNMB with a higher risk for Parkinson’s disease (PD) [ 17 ]. However, follow-up studies with independent cohorts of patients did not corroborate these initial findings [ 56 , 57 ]. Given the involvement of GPNMB in other neurodegenerative diseases besides AD, it is unlikely to serve as a disease-specific biomarker.…”

Section: Discussionmentioning

confidence: 99%

Glycoprotein NMB: a novel Alzheimer’s disease associated marker expressed in a subset of activated microglia

Hüttenrauch

Ogorek

Klafki

et al. 2018

acta neuropathol commun

113

View full text Add to dashboard Cite

Alzheimer’s disease (AD) is an irreversible, devastating neurodegenerative brain disorder characterized by the loss of neurons and subsequent cognitive decline. Despite considerable progress in the understanding of the pathophysiology of AD, the precise molecular mechanisms that cause the disease remain elusive. By now, there is ample evidence that activated microglia have a critical role in the initiation and progression of AD. The present study describes the identification of Glycoprotein nonmetastatic melanoma protein B (GPNMB) as a novel AD-related factor in both transgenic mice and sporadic AD patients by expression profiling, immunohistochemistry and ELISA measurements. We show that GPNMB levels increase in an age-dependent manner in transgenic AD models showing profound cerebral neuron loss and demonstrate that GPNMB co-localizes with a distinct population of IBA1-positive microglia cells that cluster around amyloid plaques. Our data further indicate that GPNMB is part of a microglia activation state that is only present under neurodegenerative conditions and that is characterized by the up-regulation of a subset of genes including TREM2, APOE and CST7. In agreement, we provide in vitro evidence that soluble Aβ has a direct effect on GPNMB expression in an immortalized microglia cell line. Importantly, we show for the first time that GPNMB is elevated in brain samples and cerebrospinal fluid (CSF) of sporadic AD patients when compared to non-demented controls.The current findings indicate that GPNMB represents a novel disease-associated marker that appears to play a role in the neuroinflammatory response of AD.Electronic supplementary materialThe online version of this article (10.1186/s40478-018-0612-3) contains supplementary material, which is available to authorized users.

show abstract

Section: Discussionmentioning

confidence: 99%

Glycoprotein NMB: a novel Alzheimer’s disease associated marker expressed in a subset of activated microglia

Hüttenrauch

Ogorek

Klafki

et al. 2018

acta neuropathol commun

113

View full text Add to dashboard Cite

show abstract

“…It is of note that a GWAS conducted in PD, amyotrophic lateral sclerosis (ALS), and multiple system atrophy (MSA) cohorts from a Han Chinese population reported that GPNMB has no association of rs156429, which is located in intron 6–7 of GPNMB gene, Chr7:23,266,401, with PD; this SNP is in strong LD with rs199347, suggesting that either the association is population specific or indicating the need of meta-analyses in large cohorts in order to eradicate false negative results [27]. …”

Section: Discussionmentioning

confidence: 99%

Increased brain expression of GPNMB is associated with genome wide significant risk for Parkinson’s disease on chromosome 7p15.3

Murthy

Blauwendraat²,

Ukbec

et al. 2017

Neurogenetics

View full text Add to dashboard Cite

Genome wide association studies (GWAS) for Parkinson’s disease (PD) have previously revealed a significant association with a locus on chromosome 7p15.3, initially designated as the glycoprotein non-metastatic melanoma protein B (GPNMB) locus. In this study, the functional consequences of this association on expression were explored in depth by integrating different expression quantitative trait locus (eQTL) datasets (Braineac, CAGEseq, GTEx, and Phenotype-Genotype Integrator (PheGenI)). Top risk SNP rs199347 eQTLs demonstrated increased expressions of GPNMB, KLHL7, and NUPL2 with the major allele (AA) in brain, with most significant eQTLs in cortical regions, followed by putamen. In addition, decreased expression of the antisense RNA KLHL7-AS1 was observed in GTEx. Furthermore, rs199347 is an eQTL with long non-coding RNA (AC005082.12) in human tissues other than brain. Interestingly, transcript-specific eQTLs in immune-related tissues (spleen and lymphoblastoid cells) for NUPL2 and KLHL7-AS1 were observed, which suggests a complex functional role of this eQTL in specific tissues, cell types at specific time points. Significantly increased expression of GPNMB linked to rs199347 was consistent across all datasets, and taken in combination with the risk SNP being located within the GPNMB gene, these results suggest that increased expression of GPNMB is the causative link explaining the association of this locus with PD. However, other transcript eQTLs and subsequent functional roles cannot be excluded. This highlights the importance of further investigations to understand the functional interactions between the coding genes, antisense, and non-coding RNA species considering the tissue and cell-type specificity to understand the underlying biological mechanisms in PD.Electronic supplementary materialThe online version of this article (doi:10.1007/s10048-017-0514-8) contains supplementary material, which is available to authorized users.

show abstract

“…One study revealed that rs156429 was associated with motor traits in older populations with mild parkinsonian signs (Shulman et al, 2014 ). Another result suggested that this SNP had no association with anxiety and depression symptoms in PD patients (Xu et al, 2016 ). As for gender factor, previous literature reported that GPNMB rs156429 might have a protective role in male Chinese PD patients (Liu et al, 2015 ).…”

Section: Discussionmentioning

confidence: 99%

“…In Liu's report, there were significant differences between male Chinese PD participants and healthy controls in both genotype ( p = 0.01) and allele distribution ( p = 0.01, OR = 0.67) of rs156429, indicating that GPNMB rs156429 could have a protective role in male Chinese patients with PD (Liu et al, 2015 ). However, results were inconsistent in other European-descended populations (Hernandez et al, 2012 ; Soto-Ortolaza et al, 2013 ; Kara et al, 2014 ) and the southwestern Chinese population (Xu et al, 2016 ), which failed to find the association of GPNMB rs156429 with PD. More related clinical studies with larger sample sizes are urgently needed.…”

Section: Introductionmentioning

confidence: 92%

“…The results of one study conducted among elderly American people with mild Parkinsonian signs showed that this SNP polymorphism was associated with the number of steps taken in a timed 2.4-m gait trial (Shulman et al, 2014 ). Another study showed that rs156429 had no association with anxiety and depression symptoms in southwestern Chinese PD patients (Xu et al, 2016 ). To date, there has been no study focusing on the relationship between this SNP and detailed motor and non-motor symptoms of PD.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

The Association Analysis of GPNMB rs156429 With Clinical Manifestations in Chinese Population With Parkinson's Disease

Liu

et al. 2020

Front. Genet.

View full text Add to dashboard Cite

Background: The mechanisms of Parkinson's disease (PD) include complicated genetic factors. The roles of newly found risk genes need to be further verified among different ethnicities. In a two-stage meta-analysis, single nucleotide polymorphism (SNP) of rs156429 in glycoprotein non-metastatic melanoma protein B ( GPNMB ) was reported to be associated with PD. So far clinical studies have focused on association between rs156429 and PD onset, however there is little evidence linking rs156429 with PD symptoms. Objective: This study aimed to investigate the possible association of GPNMB rs156429 with PD manifestations among southeastern Chinese people. Methods: Demographic variables, disease-related factors, and motor and non-motor assessments of 511 PD patients were collected. Polymerase chain reaction (PCR) and SNaPshot technique were used to detect GPNMB rs156429. The associations of rs156429 with PD rating scales and clinical manifestations were analyzed by Kruskal-Wallis test and logistic regression model separately. Results: Kruskal-Wallis test and logistic regression model failed to reveal an association between GPNMB rs156429 and scores from Montreal Cognitive Assessment (MoCA) ( p = 0.037; p = 1.000 after correction), and pain symptoms of 511 PD patients ( p = 0.008, OR = 0.59, 95% CI = 0.40–0.87, overdominant model after adjustment; p = 0.168 after correction, overdominant model after adjustment). However, further analysis based on genders showed that GPNMB rs156429 might have a trend for being associated with cognitive dysfunction (Mini-Mental State Examination (MMSE), p = 0.064 after correction; MoCA, p = 0.064 after correction) and pain symptoms ( p = 0.063 after correction, overdominant model after adjustment) in female PD patients but not male patients. Conclusions: This study revealed that GPNMB rs156429 might have a trend for being associated with cognitive dysfunction and pain symptoms of female PD patients in the southeastern Chinese population. Further studies from a larger sample size are needed to confirm these findings.

show abstract

No association of GPNMB rs156429 polymorphism with Parkinson’s disease, amyotrophic lateral sclerosis and multiple system atrophy in Chinese population

Cited by 14 publications

References 27 publications

Glycoprotein NMB: a novel Alzheimer’s disease associated marker expressed in a subset of activated microglia

Glycoprotein NMB: a novel Alzheimer’s disease associated marker expressed in a subset of activated microglia

Increased brain expression of GPNMB is associated with genome wide significant risk for Parkinson’s disease on chromosome 7p15.3

The Association Analysis of GPNMB rs156429 With Clinical Manifestations in Chinese Population With Parkinson's Disease

Contact Info

Product

Resources

About