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Genetics of Neurogenic Orthostatic Hypotension in Parkinson’s Disease, Results from a Cross-Sectional In Silico Study

The genetic basis of Neurogenic Orthostatic Hypotension (NOH) in Parkinson’s disease (PD) has been inadequately explored. In a cross-sectional study, we examined the association between NOH and PD-related single-nucleotide polymorphisms (SNPs) and mapped their effects on gene expression and metaboli...

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Autores principales: Chevalier, Guenson, Udovin, Lucas, Otero-Losada, Matilde, Bordet, Sofia, Capani, Francisco, Luo, Sheng, Goetz, Christopher G., Perez-Lloret, Santiago
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10046202/
https://www.ncbi.nlm.nih.gov/pubmed/36979316
http://dx.doi.org/10.3390/brainsci13030506
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author Chevalier, Guenson
Udovin, Lucas
Otero-Losada, Matilde
Bordet, Sofia
Capani, Francisco
Luo, Sheng
Goetz, Christopher G.
Perez-Lloret, Santiago
author_facet Chevalier, Guenson
Udovin, Lucas
Otero-Losada, Matilde
Bordet, Sofia
Capani, Francisco
Luo, Sheng
Goetz, Christopher G.
Perez-Lloret, Santiago
author_sort Chevalier, Guenson
collection PubMed
description The genetic basis of Neurogenic Orthostatic Hypotension (NOH) in Parkinson’s disease (PD) has been inadequately explored. In a cross-sectional study, we examined the association between NOH and PD-related single-nucleotide polymorphisms (SNPs) and mapped their effects on gene expression and metabolic and signaling pathways. Patients with PD, free from pathological conditions associated with OH, and not taking OH-associated medications were included. NOH was defined as per international guidelines. Logistic regression was used to relate SNPs to NOH. Linkage-disequilibrium analysis, expression quantitative trait loci, and enrichment analysis were used to assess the effects on gene expression and metabolic/signaling pathways. We included 304 PD patients in the study, 35 of whom had NOH (11.5%). NOH was more frequent in patients with SNPs in SNCA, TMEM175, FAM47E-STBD1, CCDC62, SCN3A, MIR4696, SH3GL2, and LZTS3/DDRGK1 and less frequent in those with SNPs in ITGA8, IP6K2, SIPA1L2, NDUFAF2. These SNPs affected gene expression associated with the significant hierarchical central structures of the autonomic nervous system. They influenced several metabolic/signaling pathways, most notably IP3/Ca++ signaling, the PKA-CREB pathway, and the metabolism of fatty acids. These findings provide new insights into the pathophysiology of NOH in PD and may provide targets for future therapies.
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spelling pubmed-100462022023-03-29 Genetics of Neurogenic Orthostatic Hypotension in Parkinson’s Disease, Results from a Cross-Sectional In Silico Study Chevalier, Guenson Udovin, Lucas Otero-Losada, Matilde Bordet, Sofia Capani, Francisco Luo, Sheng Goetz, Christopher G. Perez-Lloret, Santiago Brain Sci Article The genetic basis of Neurogenic Orthostatic Hypotension (NOH) in Parkinson’s disease (PD) has been inadequately explored. In a cross-sectional study, we examined the association between NOH and PD-related single-nucleotide polymorphisms (SNPs) and mapped their effects on gene expression and metabolic and signaling pathways. Patients with PD, free from pathological conditions associated with OH, and not taking OH-associated medications were included. NOH was defined as per international guidelines. Logistic regression was used to relate SNPs to NOH. Linkage-disequilibrium analysis, expression quantitative trait loci, and enrichment analysis were used to assess the effects on gene expression and metabolic/signaling pathways. We included 304 PD patients in the study, 35 of whom had NOH (11.5%). NOH was more frequent in patients with SNPs in SNCA, TMEM175, FAM47E-STBD1, CCDC62, SCN3A, MIR4696, SH3GL2, and LZTS3/DDRGK1 and less frequent in those with SNPs in ITGA8, IP6K2, SIPA1L2, NDUFAF2. These SNPs affected gene expression associated with the significant hierarchical central structures of the autonomic nervous system. They influenced several metabolic/signaling pathways, most notably IP3/Ca++ signaling, the PKA-CREB pathway, and the metabolism of fatty acids. These findings provide new insights into the pathophysiology of NOH in PD and may provide targets for future therapies. MDPI 2023-03-17 /pmc/articles/PMC10046202/ /pubmed/36979316 http://dx.doi.org/10.3390/brainsci13030506 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Chevalier, Guenson
Udovin, Lucas
Otero-Losada, Matilde
Bordet, Sofia
Capani, Francisco
Luo, Sheng
Goetz, Christopher G.
Perez-Lloret, Santiago
Genetics of Neurogenic Orthostatic Hypotension in Parkinson’s Disease, Results from a Cross-Sectional In Silico Study
title Genetics of Neurogenic Orthostatic Hypotension in Parkinson’s Disease, Results from a Cross-Sectional In Silico Study
title_full Genetics of Neurogenic Orthostatic Hypotension in Parkinson’s Disease, Results from a Cross-Sectional In Silico Study
title_fullStr Genetics of Neurogenic Orthostatic Hypotension in Parkinson’s Disease, Results from a Cross-Sectional In Silico Study
title_full_unstemmed Genetics of Neurogenic Orthostatic Hypotension in Parkinson’s Disease, Results from a Cross-Sectional In Silico Study
title_short Genetics of Neurogenic Orthostatic Hypotension in Parkinson’s Disease, Results from a Cross-Sectional In Silico Study
title_sort genetics of neurogenic orthostatic hypotension in parkinson’s disease, results from a cross-sectional in silico study
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10046202/
https://www.ncbi.nlm.nih.gov/pubmed/36979316
http://dx.doi.org/10.3390/brainsci13030506
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