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The Genetic Basis of Probable REM Sleep Behavior Disorder in Parkinson’s Disease

Patients with Parkinson’s Disease (PD) experience REM sleep behavior disorder (RBD) more frequently than healthy controls. RBD is associated with torpid disease evolution. To test the hypothesis that differential genetic signatures might contribute to the torpid disease evolution in PD patients with...

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Autores principales: Perez-Lloret, Santiago, Chevalier, Guenson, Bordet, Sofia, Barbar, Hanny, Capani, Francisco, Udovin, Lucas, Otero-Losada, Matilde
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10452689/
https://www.ncbi.nlm.nih.gov/pubmed/37626502
http://dx.doi.org/10.3390/brainsci13081146
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author Perez-Lloret, Santiago
Chevalier, Guenson
Bordet, Sofia
Barbar, Hanny
Capani, Francisco
Udovin, Lucas
Otero-Losada, Matilde
author_facet Perez-Lloret, Santiago
Chevalier, Guenson
Bordet, Sofia
Barbar, Hanny
Capani, Francisco
Udovin, Lucas
Otero-Losada, Matilde
author_sort Perez-Lloret, Santiago
collection PubMed
description Patients with Parkinson’s Disease (PD) experience REM sleep behavior disorder (RBD) more frequently than healthy controls. RBD is associated with torpid disease evolution. To test the hypothesis that differential genetic signatures might contribute to the torpid disease evolution in PD patients with RBD we compared the rate of genetic mutations in PD patients with or without probable RBD. Patients with a clinical diagnosis of PD in the Parkinson’s Progression Markers Initiative (PPMI) database entered the study. We excluded those with missing data, dementia, psychiatric conditions, or a diagnosis change over the first five years from the initial PD diagnosis. Probable RBD (pRBD) was confirmed by a REM Sleep Behavior Disorder Screening Questionnaire score > 5 points. Logistic regression and Machine Learning (ML) algorithms were used to relate Single Nucleotide Polymorphism (SNPs) in PD-related genes with pRBD. We included 330 PD patients fulfilling all inclusion and exclusion criteria. The final logistic multivariate model revealed that the following SNPs increased the risk of pRBD: GBA_N370S_rs76763715 (OR, 95% CI: 3.38, 1.45–7.93), SNCA_A53T_rs104893877 (8.21, 2.26–36.34), ANK2. CAMK2D_rs78738012 (2.12, 1.08–4.10), and ZNF184_rs9468199 (1.89, 1.08–3.33). Conversely, SNP COQ7. SYT17_rs11343 reduced pRBD risk (0.36, 0.15–0.78). The ML algorithms led to similar results. The predictive models were highly specific (95–99%) but lacked sensitivity (9–39%). We found a distinctive genetic signature for pRBD in PD. The high specificity and low sensitivity of the predictive models suggest that genetic mutations are necessary but not sufficient to develop pRBD in PD. Additional investigations are needed.
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spelling pubmed-104526892023-08-26 The Genetic Basis of Probable REM Sleep Behavior Disorder in Parkinson’s Disease Perez-Lloret, Santiago Chevalier, Guenson Bordet, Sofia Barbar, Hanny Capani, Francisco Udovin, Lucas Otero-Losada, Matilde Brain Sci Article Patients with Parkinson’s Disease (PD) experience REM sleep behavior disorder (RBD) more frequently than healthy controls. RBD is associated with torpid disease evolution. To test the hypothesis that differential genetic signatures might contribute to the torpid disease evolution in PD patients with RBD we compared the rate of genetic mutations in PD patients with or without probable RBD. Patients with a clinical diagnosis of PD in the Parkinson’s Progression Markers Initiative (PPMI) database entered the study. We excluded those with missing data, dementia, psychiatric conditions, or a diagnosis change over the first five years from the initial PD diagnosis. Probable RBD (pRBD) was confirmed by a REM Sleep Behavior Disorder Screening Questionnaire score > 5 points. Logistic regression and Machine Learning (ML) algorithms were used to relate Single Nucleotide Polymorphism (SNPs) in PD-related genes with pRBD. We included 330 PD patients fulfilling all inclusion and exclusion criteria. The final logistic multivariate model revealed that the following SNPs increased the risk of pRBD: GBA_N370S_rs76763715 (OR, 95% CI: 3.38, 1.45–7.93), SNCA_A53T_rs104893877 (8.21, 2.26–36.34), ANK2. CAMK2D_rs78738012 (2.12, 1.08–4.10), and ZNF184_rs9468199 (1.89, 1.08–3.33). Conversely, SNP COQ7. SYT17_rs11343 reduced pRBD risk (0.36, 0.15–0.78). The ML algorithms led to similar results. The predictive models were highly specific (95–99%) but lacked sensitivity (9–39%). We found a distinctive genetic signature for pRBD in PD. The high specificity and low sensitivity of the predictive models suggest that genetic mutations are necessary but not sufficient to develop pRBD in PD. Additional investigations are needed. MDPI 2023-07-30 /pmc/articles/PMC10452689/ /pubmed/37626502 http://dx.doi.org/10.3390/brainsci13081146 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Perez-Lloret, Santiago
Chevalier, Guenson
Bordet, Sofia
Barbar, Hanny
Capani, Francisco
Udovin, Lucas
Otero-Losada, Matilde
The Genetic Basis of Probable REM Sleep Behavior Disorder in Parkinson’s Disease
title The Genetic Basis of Probable REM Sleep Behavior Disorder in Parkinson’s Disease
title_full The Genetic Basis of Probable REM Sleep Behavior Disorder in Parkinson’s Disease
title_fullStr The Genetic Basis of Probable REM Sleep Behavior Disorder in Parkinson’s Disease
title_full_unstemmed The Genetic Basis of Probable REM Sleep Behavior Disorder in Parkinson’s Disease
title_short The Genetic Basis of Probable REM Sleep Behavior Disorder in Parkinson’s Disease
title_sort genetic basis of probable rem sleep behavior disorder in parkinson’s disease
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10452689/
https://www.ncbi.nlm.nih.gov/pubmed/37626502
http://dx.doi.org/10.3390/brainsci13081146
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