Genetics of neurogenic orthostatic hypotension in Parkinson’s disease, results from a cross-sectional in silico study

Abstract: 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...

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Autores principales: Chevalier, Guenson, Udovin, Lucas D., Otero Losada, Matilde, Bordet, Sofía, Capani, Francisco, Luo, Sheng, Goetz, Christopher, Pérez Lloret, Santiago
Formato: Artículo
Lenguaje:Inglés
Publicado: MDPI 2023
Materias:
ENFERMEDAD DE PARKINSON
POLIMORFISMO DE NUCLEÓTIDO SIMPLE
ENFERMEDADES NEURODEGENERATIVAS
FISIOPATOLOGÍA
HIPOTENSIÓN ORTOSTÁTICA NEUROGÉNICA
Acceso en línea:https://repositorio.uca.edu.ar/handle/123456789/17348
Aporte de:
Repositorio Institucional de la Universidad Católica Argentina (UCA) de Universidad Católica Argentina
id I33-R139-123456789-17348
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spelling I33-R139-123456789-173482024-03-07T13:21:31Z Genetics of neurogenic orthostatic hypotension in Parkinson’s disease, results from a cross-sectional in silico study Chevalier, Guenson Udovin, Lucas D. Otero Losada, Matilde Bordet, Sofía Capani, Francisco Luo, Sheng Goetz, Christopher Pérez Lloret, Santiago ENFERMEDAD DE PARKINSON POLIMORFISMO DE NUCLEÓTIDO SIMPLE ENFERMEDADES NEURODEGENERATIVAS FISIOPATOLOGÍA HIPOTENSIÓN ORTOSTÁTICA NEUROGÉNICA Abstract: 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. 2023-10-24T14:51:09Z 2023-10-24T14:51:09Z 2023 Artículo Pérez Lloret, S., Chevalier, G., Udovin, L., Otero Losada, M. Genetics of neurogenic orthostatic hypotension in Parkinson’s disease, results from a cross-sectional in silico study [en línea]. Brain Sciences. 2023, 13, 506. doi: 10.3390/brainsci13030506. Disponible en: https://repositorio.uca.edu.ar/handle/123456789/17348 2076-3425 https://repositorio.uca.edu.ar/handle/123456789/17348 10.3390/brainsci13030506 36979316 eng Atribución-NoComercial-CompartirIgual 4.0 Internacional Acceso abierto http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf MDPI Brain Sciences. 2023, 13, 506
institution Universidad Católica Argentina
institution_str I-33
repository_str R-139
collection Repositorio Institucional de la Universidad Católica Argentina (UCA)
language Inglés
topic ENFERMEDAD DE PARKINSON
POLIMORFISMO DE NUCLEÓTIDO SIMPLE
ENFERMEDADES NEURODEGENERATIVAS
FISIOPATOLOGÍA
HIPOTENSIÓN ORTOSTÁTICA NEUROGÉNICA
spellingShingle ENFERMEDAD DE PARKINSON
POLIMORFISMO DE NUCLEÓTIDO SIMPLE
ENFERMEDADES NEURODEGENERATIVAS
FISIOPATOLOGÍA
HIPOTENSIÓN ORTOSTÁTICA NEUROGÉNICA
Chevalier, Guenson
Udovin, Lucas D.
Otero Losada, Matilde
Bordet, Sofía
Capani, Francisco
Luo, Sheng
Goetz, Christopher
Pérez Lloret, Santiago
Genetics of neurogenic orthostatic hypotension in Parkinson’s disease, results from a cross-sectional in silico study
topic_facet ENFERMEDAD DE PARKINSON
POLIMORFISMO DE NUCLEÓTIDO SIMPLE
ENFERMEDADES NEURODEGENERATIVAS
FISIOPATOLOGÍA
HIPOTENSIÓN ORTOSTÁTICA NEUROGÉNICA
description Abstract: 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.
format Artículo
author Chevalier, Guenson
Udovin, Lucas D.
Otero Losada, Matilde
Bordet, Sofía
Capani, Francisco
Luo, Sheng
Goetz, Christopher
Pérez Lloret, Santiago
author_facet Chevalier, Guenson
Udovin, Lucas D.
Otero Losada, Matilde
Bordet, Sofía
Capani, Francisco
Luo, Sheng
Goetz, Christopher
Pérez Lloret, Santiago
author_sort Chevalier, Guenson
title 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_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
publisher MDPI
publishDate 2023
url https://repositorio.uca.edu.ar/handle/123456789/17348
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