{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T20:54:48Z","timestamp":1790456088752,"version":"4.1.0"},"reference-count":47,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2023,3,17]],"date-time":"2023-03-17T00:00:00Z","timestamp":1679011200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain Sciences"],"abstract":"<jats:p>The genetic basis of Neurogenic Orthostatic Hypotension (NOH) in Parkinson\u2019s 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.<\/jats:p>","DOI":"10.3390\/brainsci13030506","type":"journal-article","created":{"date-parts":[[2023,3,17]],"date-time":"2023-03-17T05:06:01Z","timestamp":1679029561000},"page":"506","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Genetics of Neurogenic Orthostatic Hypotension in Parkinson\u2019s Disease, Results from a Cross-Sectional In Silico Study"],"prefix":"10.3390","volume":"13","author":[{"given":"Guenson","family":"Chevalier","sequence":"first","affiliation":[{"name":"Centro de Altos Estudios en Ciencias Humanas y de la Salud, Universidad Abierta Interamericana, Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas, CAECIHS, UAI-CONICET, Av. Montes de Oca 745, Buenos Aires C1147AAU, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucas","family":"Udovin","sequence":"additional","affiliation":[{"name":"Centro de Altos Estudios en Ciencias Humanas y de la Salud, Universidad Abierta Interamericana, Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas, CAECIHS, UAI-CONICET, Av. Montes de Oca 745, Buenos Aires C1147AAU, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matilde","family":"Otero-Losada","sequence":"additional","affiliation":[{"name":"Centro de Altos Estudios en Ciencias Humanas y de la Salud, Universidad Abierta Interamericana, Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas, CAECIHS, UAI-CONICET, Av. Montes de Oca 745, Buenos Aires C1147AAU, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sofia","family":"Bordet","sequence":"additional","affiliation":[{"name":"Centro de Altos Estudios en Ciencias Humanas y de la Salud, Universidad Abierta Interamericana, Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas, CAECIHS, UAI-CONICET, Av. Montes de Oca 745, Buenos Aires C1147AAU, Argentina"},{"name":"Centro de Investigaciones en Psicolog\u00eda y Psicopedagog\u00eda (CIPP), Facultad de Psicolog\u00eda y Psicopedagog\u00eda, Pontificia Universidad Cat\u00f3lica Argentina (UCA), Av. Montes de Oca 745, Buenos Aires C1107AFB, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0342-0628","authenticated-orcid":false,"given":"Francisco","family":"Capani","sequence":"additional","affiliation":[{"name":"Centro de Altos Estudios en Ciencias Humanas y de la Salud, Universidad Abierta Interamericana, Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas, CAECIHS, UAI-CONICET, Av. Montes de Oca 745, Buenos Aires C1147AAU, Argentina"},{"name":"Instituto de Ciencias Biom\u00e9dicas, Facultad de Ciencias de la Salud, Universidad Aut\u00f3noma de Chile, 7500912 Santiago, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4214-5809","authenticated-orcid":false,"given":"Sheng","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Biostatistics & Bioinformatics, Duke University, Durham, NC 27708, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher G.","family":"Goetz","sequence":"additional","affiliation":[{"name":"Department of Neurological Sciences, Rush University Medical Center, Chicago, IL 60612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9069-6512","authenticated-orcid":false,"given":"Santiago","family":"Perez-Lloret","sequence":"additional","affiliation":[{"name":"Observatorio de Salud P\u00fablica, Vicerrectorado de Investigaci\u00f3n e Innovaci\u00f3n Acad\u00e9mica, Pontificia Universidad Cat\u00f3lica Argentina, Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas (UCA-CONICET), Av. Alicia Moreau de Justo 1300, Buenos Aires C1107AAZ, Argentina"},{"name":"Departamento de Fisiolog\u00eda, Facultad de Medicina, Universidad de Buenos Aires (UBA), Buenos Aires C1121ABG, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1212\/01.wnl.0000247740.47667.03","article-title":"Projected Number of People with P Disease in the Most Populous Nations, 2005 through 2030","volume":"68","author":"Dorsey","year":"2007","journal-title":"Neurology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"660","DOI":"10.1002\/mds.27360","article-title":"Disease Modification in Parkinson\u2019s Disease: Current Approaches, Challenges, and Future Considerations","volume":"33","author":"Lang","year":"2018","journal-title":"Mov. 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