dc.creatorChevalier, Guenson
dc.creatorUdovin, Lucas
dc.creatorOtero-Losada, Matilde
dc.creatorBordet, Sofia
dc.creatorCapani, Francisco
dc.creatorLuo, Sheng
dc.creatorGoetz, Christopher G.
dc.creatorPerez-Lloret, Santiago
dc.date2024-04-10T01:36:33Z
dc.date2024-04-10T01:36:33Z
dc.date2023
dc.date.accessioned2024-07-17T21:11:39Z
dc.date.available2024-07-17T21:11:39Z
dc.identifier10.3390/brainsci13030506
dc.identifier20763425
dc.identifierhttps://hdl.handle.net/20.500.12728/10639
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/9509128
dc.descriptionThe 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 by the authors.
dc.formatapplication/pdf
dc.languageen
dc.publisherMDPI
dc.subjectneurogenic orthostatic hypotension
dc.subjectParkinson’s disease
dc.subjectpathophysiology
dc.subjectPD-related variants
dc.subjectsingle-nucleotide polymorphism
dc.titleGenetics of Neurogenic Orthostatic Hypotension in Parkinson’s Disease, Results from a Cross-Sectional In Silico Study
dc.typeArticle


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