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Bioinformatics analysis and identification of genes and molecular pathways involved in Parkinson’s disease in patients with mutations in the glucocerebrosidase gene

Glucocerebrosidase (GBA) mutations occur frequently in Parkinson’s disease (PD) patients. This study aims to identify potential crucial genes and pathways associated with GBA mutations in patients with PD and to further analyze new molecular mechanisms related to the occurrence of gene mutations fro...

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Autores principales: Xu, Dan-Dan, Li, Guo-Qian, Wu, Zhi-Sheng, Liu, Xiao-Qiang, Yang, Xiao-Xia, Wang, Jie-Hua
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Lippincott Williams & Wilkins 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8253507/
https://www.ncbi.nlm.nih.gov/pubmed/34132705
http://dx.doi.org/10.1097/WNR.0000000000001685
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author Xu, Dan-Dan
Li, Guo-Qian
Wu, Zhi-Sheng
Liu, Xiao-Qiang
Yang, Xiao-Xia
Wang, Jie-Hua
author_facet Xu, Dan-Dan
Li, Guo-Qian
Wu, Zhi-Sheng
Liu, Xiao-Qiang
Yang, Xiao-Xia
Wang, Jie-Hua
author_sort Xu, Dan-Dan
collection PubMed
description Glucocerebrosidase (GBA) mutations occur frequently in Parkinson’s disease (PD) patients. This study aims to identify potential crucial genes and pathways associated with GBA mutations in patients with PD and to further analyze new molecular mechanisms related to the occurrence of gene mutations from the perspective of bioinformatics. Gene expression profiles of datasets GSE53424 and GSE99142 were acquired from the Gene Expression Ominibus database. Differentially expressed genes (DEGs) were detected, using the ‘limma’ package in R, comparing IDI-PD 1 (idiopathic PD patients) and GBA-PD 1 [PD patients with heterozygous GBA mutations (GBA N370S)] group samples. The functions of top modules were assessed using the DAVID, whereas gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed. Protein–protein interaction networks were assembled with Cytoscape software and separated into subnetworks using the Molecular Complex Detection Algorithm. Data from GSE53424 and GSE99142 were also extracted to verify our findings. There were 283 DEGs identified in PD patients heterozygous for GBA mutations. Module analysis revealed that GBA mutations in PD patients were associated with significant pathways, including Calcium signaling pathway, Rap1 signaling pathway and Cytokine–cytokine receptor interaction. Hub genes of the two modules were corticotropin-releasing hormone (CRH) and Melatonin receptor 1B (MTNR1B). The expression of CRH was downregulated, whereas that of MTNR1B was upregulated in PD patients with GBA mutations. The expression of CRH and MTNR1B has diagnostic value for PD patients with heterozygous GBA mutations. Novel DEGs and pathways identified herein might provide new insights into the underlying molecular mechanisms of heterozygous GBA mutations in PD patients.
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spelling pubmed-82535072021-07-08 Bioinformatics analysis and identification of genes and molecular pathways involved in Parkinson’s disease in patients with mutations in the glucocerebrosidase gene Xu, Dan-Dan Li, Guo-Qian Wu, Zhi-Sheng Liu, Xiao-Qiang Yang, Xiao-Xia Wang, Jie-Hua Neuroreport Cellular, Molecular and Developmental Neuroscience Glucocerebrosidase (GBA) mutations occur frequently in Parkinson’s disease (PD) patients. This study aims to identify potential crucial genes and pathways associated with GBA mutations in patients with PD and to further analyze new molecular mechanisms related to the occurrence of gene mutations from the perspective of bioinformatics. Gene expression profiles of datasets GSE53424 and GSE99142 were acquired from the Gene Expression Ominibus database. Differentially expressed genes (DEGs) were detected, using the ‘limma’ package in R, comparing IDI-PD 1 (idiopathic PD patients) and GBA-PD 1 [PD patients with heterozygous GBA mutations (GBA N370S)] group samples. The functions of top modules were assessed using the DAVID, whereas gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed. Protein–protein interaction networks were assembled with Cytoscape software and separated into subnetworks using the Molecular Complex Detection Algorithm. Data from GSE53424 and GSE99142 were also extracted to verify our findings. There were 283 DEGs identified in PD patients heterozygous for GBA mutations. Module analysis revealed that GBA mutations in PD patients were associated with significant pathways, including Calcium signaling pathway, Rap1 signaling pathway and Cytokine–cytokine receptor interaction. Hub genes of the two modules were corticotropin-releasing hormone (CRH) and Melatonin receptor 1B (MTNR1B). The expression of CRH was downregulated, whereas that of MTNR1B was upregulated in PD patients with GBA mutations. The expression of CRH and MTNR1B has diagnostic value for PD patients with heterozygous GBA mutations. Novel DEGs and pathways identified herein might provide new insights into the underlying molecular mechanisms of heterozygous GBA mutations in PD patients. Lippincott Williams & Wilkins 2021-06-14 2021-08-04 /pmc/articles/PMC8253507/ /pubmed/34132705 http://dx.doi.org/10.1097/WNR.0000000000001685 Text en Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (https://creativecommons.org/licenses/by-nc-nd/4.0/) (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.
spellingShingle Cellular, Molecular and Developmental Neuroscience
Xu, Dan-Dan
Li, Guo-Qian
Wu, Zhi-Sheng
Liu, Xiao-Qiang
Yang, Xiao-Xia
Wang, Jie-Hua
Bioinformatics analysis and identification of genes and molecular pathways involved in Parkinson’s disease in patients with mutations in the glucocerebrosidase gene
title Bioinformatics analysis and identification of genes and molecular pathways involved in Parkinson’s disease in patients with mutations in the glucocerebrosidase gene
title_full Bioinformatics analysis and identification of genes and molecular pathways involved in Parkinson’s disease in patients with mutations in the glucocerebrosidase gene
title_fullStr Bioinformatics analysis and identification of genes and molecular pathways involved in Parkinson’s disease in patients with mutations in the glucocerebrosidase gene
title_full_unstemmed Bioinformatics analysis and identification of genes and molecular pathways involved in Parkinson’s disease in patients with mutations in the glucocerebrosidase gene
title_short Bioinformatics analysis and identification of genes and molecular pathways involved in Parkinson’s disease in patients with mutations in the glucocerebrosidase gene
title_sort bioinformatics analysis and identification of genes and molecular pathways involved in parkinson’s disease in patients with mutations in the glucocerebrosidase gene
topic Cellular, Molecular and Developmental Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8253507/
https://www.ncbi.nlm.nih.gov/pubmed/34132705
http://dx.doi.org/10.1097/WNR.0000000000001685
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