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

Autores
Chevalier, Guenson; Udovin, Lucas; Otero-losada, Matilde Estela; Bordet, Sofía; Capani, Francisco; Luo, Sheng; Goetz, Christopher G.; Perez Lloret, Santiago
Año de publicación
2023
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
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.
Fil: Chevalier, Guenson. Universidad Abierta Interamericana; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Udovin, Lucas. Universidad Abierta Interamericana; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Otero-losada, Matilde Estela. Universidad Abierta Interamericana; Argentina. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Bordet, Sofía. Universidad Abierta Interamericana; Argentina. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Capani, Francisco. Universidad Abierta Interamericana; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Luo, Sheng. University of Duke; Estados Unidos
Fil: Goetz, Christopher G.. Rush University Medical Center; Estados Unidos
Fil: Perez Lloret, Santiago. Universidad de Buenos Aires; Argentina. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Materia
NEUROGENIC ORTHOSTATIC HYPOTENSION
PARKINSON’S DISEASE
PATHOPHYSIOLOGY
PD-RELATED VARIANTS
SINGLE-NUCLEOTIDE POLYMORPHISM
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/219613
Acceder
id CONICETDig_c3a5e62bb7f3bf4a8575d1c550820693
oai_identifier_str oai:ri.conicet.gov.ar:11336/219613
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Genetics of Neurogenic Orthostatic Hypotension in Parkinson’s Disease, Results from a Cross-Sectional In Silico StudyChevalier, GuensonUdovin, LucasOtero-losada, Matilde EstelaBordet, SofíaCapani, FranciscoLuo, ShengGoetz, Christopher G.Perez Lloret, SantiagoNEUROGENIC ORTHOSTATIC HYPOTENSIONPARKINSON’S DISEASEPATHOPHYSIOLOGYPD-RELATED VARIANTSSINGLE-NUCLEOTIDE POLYMORPHISMhttps://purl.org/becyt/ford/3.2https://purl.org/becyt/ford/3The 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.Fil: Chevalier, Guenson. Universidad Abierta Interamericana; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Udovin, Lucas. Universidad Abierta Interamericana; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Otero-losada, Matilde Estela. Universidad Abierta Interamericana; Argentina. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Bordet, Sofía. Universidad Abierta Interamericana; Argentina. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Capani, Francisco. Universidad Abierta Interamericana; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Luo, Sheng. University of Duke; Estados UnidosFil: Goetz, Christopher G.. Rush University Medical Center; Estados UnidosFil: Perez Lloret, Santiago. Universidad de Buenos Aires; Argentina. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaMDPI2023-03info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/219613Chevalier, Guenson; Udovin, Lucas; Otero-losada, Matilde Estela; Bordet, Sofía; Capani, Francisco; et al.; Genetics of Neurogenic Orthostatic Hypotension in Parkinson’s Disease, Results from a Cross-Sectional In Silico Study; MDPI; Brain Sciences; 13; 3; 3-2023; 1-122076-3425CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.3390/brainsci13030506info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:10:32Zoai:ri.conicet.gov.ar:11336/219613instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 10:10:33.153CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv 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
spellingShingle Genetics of Neurogenic Orthostatic Hypotension in Parkinson’s Disease, Results from a Cross-Sectional In Silico Study
Chevalier, Guenson
NEUROGENIC ORTHOSTATIC HYPOTENSION
PARKINSON’S DISEASE
PATHOPHYSIOLOGY
PD-RELATED VARIANTS
SINGLE-NUCLEOTIDE POLYMORPHISM
title_short 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_sort Genetics of Neurogenic Orthostatic Hypotension in Parkinson’s Disease, Results from a Cross-Sectional In Silico Study
dc.creator.none.fl_str_mv Chevalier, Guenson
Udovin, Lucas
Otero-losada, Matilde Estela
Bordet, Sofía
Capani, Francisco
Luo, Sheng
Goetz, Christopher G.
Perez Lloret, Santiago
author Chevalier, Guenson
author_facet Chevalier, Guenson
Udovin, Lucas
Otero-losada, Matilde Estela
Bordet, Sofía
Capani, Francisco
Luo, Sheng
Goetz, Christopher G.
Perez Lloret, Santiago
author_role author
author2 Udovin, Lucas
Otero-losada, Matilde Estela
Bordet, Sofía
Capani, Francisco
Luo, Sheng
Goetz, Christopher G.
Perez Lloret, Santiago
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv NEUROGENIC ORTHOSTATIC HYPOTENSION
PARKINSON’S DISEASE
PATHOPHYSIOLOGY
PD-RELATED VARIANTS
SINGLE-NUCLEOTIDE POLYMORPHISM
topic NEUROGENIC ORTHOSTATIC HYPOTENSION
PARKINSON’S DISEASE
PATHOPHYSIOLOGY
PD-RELATED VARIANTS
SINGLE-NUCLEOTIDE POLYMORPHISM
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.2
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv 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.
Fil: Chevalier, Guenson. Universidad Abierta Interamericana; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Udovin, Lucas. Universidad Abierta Interamericana; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Otero-losada, Matilde Estela. Universidad Abierta Interamericana; Argentina. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Bordet, Sofía. Universidad Abierta Interamericana; Argentina. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Capani, Francisco. Universidad Abierta Interamericana; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Luo, Sheng. University of Duke; Estados Unidos
Fil: Goetz, Christopher G.. Rush University Medical Center; Estados Unidos
Fil: Perez Lloret, Santiago. Universidad de Buenos Aires; Argentina. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
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.
publishDate 2023
dc.date.none.fl_str_mv 2023-03
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/219613
Chevalier, Guenson; Udovin, Lucas; Otero-losada, Matilde Estela; Bordet, Sofía; Capani, Francisco; et al.; Genetics of Neurogenic Orthostatic Hypotension in Parkinson’s Disease, Results from a Cross-Sectional In Silico Study; MDPI; Brain Sciences; 13; 3; 3-2023; 1-12
2076-3425
CONICET Digital
CONICET
url http://hdl.handle.net/11336/219613
identifier_str_mv Chevalier, Guenson; Udovin, Lucas; Otero-losada, Matilde Estela; Bordet, Sofía; Capani, Francisco; et al.; Genetics of Neurogenic Orthostatic Hypotension in Parkinson’s Disease, Results from a Cross-Sectional In Silico Study; MDPI; Brain Sciences; 13; 3; 3-2023; 1-12
2076-3425
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.3390/brainsci13030506
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.069144

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