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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MDPI AG
2023-03-01
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| Series: | Brain Sciences |
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| Online Access: | https://www.mdpi.com/2076-3425/13/3/506 |
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| author | Guenson Chevalier Lucas Udovin Matilde Otero-Losada Sofia Bordet Francisco Capani Sheng Luo Christopher G. Goetz Santiago Perez-Lloret |
| author_facet | Guenson Chevalier Lucas Udovin Matilde Otero-Losada Sofia Bordet Francisco Capani Sheng Luo Christopher G. Goetz Santiago Perez-Lloret |
| author_sort | Guenson Chevalier |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-11T06:51:09Z |
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| id | doaj.art-f8a7a5122b7d44cdbc7ce41e79036c27 |
| institution | Directory Open Access Journal |
| issn | 2076-3425 |
| language | English |
| last_indexed | 2024-03-11T06:51:09Z |
| publishDate | 2023-03-01 |
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| series | Brain Sciences |
| spelling | doaj.art-f8a7a5122b7d44cdbc7ce41e79036c272023-11-17T10:00:48ZengMDPI AGBrain Sciences2076-34252023-03-0113350610.3390/brainsci13030506Genetics of Neurogenic Orthostatic Hypotension in Parkinson’s Disease, Results from a Cross-Sectional In Silico StudyGuenson Chevalier0Lucas Udovin1Matilde Otero-Losada2Sofia Bordet3Francisco Capani4Sheng Luo5Christopher G. Goetz6Santiago Perez-Lloret7Centro de Altos Estudios en Ciencias Humanas y de la Salud, Universidad Abierta Interamericana, Consejo Nacional de Investigaciones Científicas y Técnicas, CAECIHS, UAI-CONICET, Av. Montes de Oca 745, Buenos Aires C1147AAU, ArgentinaCentro de Altos Estudios en Ciencias Humanas y de la Salud, Universidad Abierta Interamericana, Consejo Nacional de Investigaciones Científicas y Técnicas, CAECIHS, UAI-CONICET, Av. Montes de Oca 745, Buenos Aires C1147AAU, ArgentinaCentro de Altos Estudios en Ciencias Humanas y de la Salud, Universidad Abierta Interamericana, Consejo Nacional de Investigaciones Científicas y Técnicas, CAECIHS, UAI-CONICET, Av. Montes de Oca 745, Buenos Aires C1147AAU, ArgentinaCentro de Altos Estudios en Ciencias Humanas y de la Salud, Universidad Abierta Interamericana, Consejo Nacional de Investigaciones Científicas y Técnicas, CAECIHS, UAI-CONICET, Av. Montes de Oca 745, Buenos Aires C1147AAU, ArgentinaCentro de Altos Estudios en Ciencias Humanas y de la Salud, Universidad Abierta Interamericana, Consejo Nacional de Investigaciones Científicas y Técnicas, CAECIHS, UAI-CONICET, Av. Montes de Oca 745, Buenos Aires C1147AAU, ArgentinaDepartment of Biostatistics & Bioinformatics, Duke University, Durham, NC 27708, USADepartment of Neurological Sciences, Rush University Medical Center, Chicago, IL 60612, USAObservatorio de Salud Pública, Vicerrectorado de Investigación e Innovación Académica, Pontificia Universidad Católica Argentina, Consejo Nacional de Investigaciones Científicas y Técnicas (UCA-CONICET), Av. Alicia Moreau de Justo 1300, Buenos Aires C1107AAZ, ArgentinaThe 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.https://www.mdpi.com/2076-3425/13/3/506single-nucleotide polymorphismParkinson’s diseaseneurogenic orthostatic hypotensionpathophysiologyPD-related variants |
| spellingShingle | Guenson Chevalier Lucas Udovin Matilde Otero-Losada Sofia Bordet Francisco Capani Sheng Luo Christopher G. Goetz Santiago Perez-Lloret Genetics of Neurogenic Orthostatic Hypotension in Parkinson’s Disease, Results from a Cross-Sectional In Silico Study Brain Sciences single-nucleotide polymorphism Parkinson’s disease neurogenic orthostatic hypotension pathophysiology PD-related variants |
| 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 | single-nucleotide polymorphism Parkinson’s disease neurogenic orthostatic hypotension pathophysiology PD-related variants |
| url | https://www.mdpi.com/2076-3425/13/3/506 |
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