The genetic basis of probable rem sleep behavior disorder in Parkinson’s disease

Abstract: 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...

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Autores principales: Pérez Lloret, Santiago, Chevalier, Guenson, Bordet, Sofía, Barbar, Hanny, Capani, Francisco, Udovin, Lucas D., Otero Losada, Matilde
Formato: Artículo
Lenguaje:Inglés
Publicado: MDPI 2023
Materias:
ENFERMEDAD DE PARKINSON
ENFERMEDADES NEURODEGENERATIVAS
POLIMORFISMO DE NUCLEÓTIDO SIMPLE
TRASTORNOS DE LA CONDUCTA
SUEÑO REM
FISIOPATOLOGÍA
Acceso en línea:https://repositorio.uca.edu.ar/handle/123456789/17344
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Repositorio Institucional de la Universidad Católica Argentina (UCA) de Universidad Católica Argentina
id I33-R139-123456789-17344
record_format dspace
spelling I33-R139-123456789-173442023-11-23T18:03:14Z The genetic basis of probable rem sleep behavior disorder in Parkinson’s disease Pérez Lloret, Santiago Chevalier, Guenson Bordet, Sofía Barbar, Hanny Capani, Francisco Udovin, Lucas D. Otero Losada, Matilde ENFERMEDAD DE PARKINSON ENFERMEDADES NEURODEGENERATIVAS POLIMORFISMO DE NUCLEÓTIDO SIMPLE TRASTORNOS DE LA CONDUCTA SUEÑO REM FISIOPATOLOGÍA Abstract: 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. 2023-10-24T11:40:36Z 2023-10-24T11:40:36Z 2023 Artículo Perez Lloret, S., Chevalier, G., Bordet, S. et al. The genetic basis of probable rem sleep behavior disorder in Parkinson’s disease [en línea]. Brain Sciences. 2023, 13, 1146. doi: 10.3390/brainsci13081146. Disponible en: https://repositorio.uca.edu.ar/handle/123456789/17344 2076-3425 https://repositorio.uca.edu.ar/handle/123456789/17344 10.3390/brainsci13081146 37626502 eng Acceso abierto http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf MDPI Brain Sciences. 2023, 13, 1146
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
ENFERMEDADES NEURODEGENERATIVAS
POLIMORFISMO DE NUCLEÓTIDO SIMPLE
TRASTORNOS DE LA CONDUCTA
SUEÑO REM
FISIOPATOLOGÍA
spellingShingle ENFERMEDAD DE PARKINSON
ENFERMEDADES NEURODEGENERATIVAS
POLIMORFISMO DE NUCLEÓTIDO SIMPLE
TRASTORNOS DE LA CONDUCTA
SUEÑO REM
FISIOPATOLOGÍA
Pérez Lloret, Santiago
Chevalier, Guenson
Bordet, Sofía
Barbar, Hanny
Capani, Francisco
Udovin, Lucas D.
Otero Losada, Matilde
The genetic basis of probable rem sleep behavior disorder in Parkinson’s disease
topic_facet ENFERMEDAD DE PARKINSON
ENFERMEDADES NEURODEGENERATIVAS
POLIMORFISMO DE NUCLEÓTIDO SIMPLE
TRASTORNOS DE LA CONDUCTA
SUEÑO REM
FISIOPATOLOGÍA
description Abstract: 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.
format Artículo
author Pérez Lloret, Santiago
Chevalier, Guenson
Bordet, Sofía
Barbar, Hanny
Capani, Francisco
Udovin, Lucas D.
Otero Losada, Matilde
author_facet Pérez Lloret, Santiago
Chevalier, Guenson
Bordet, Sofía
Barbar, Hanny
Capani, Francisco
Udovin, Lucas D.
Otero Losada, Matilde
author_sort Pérez Lloret, Santiago
title 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_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_sort genetic basis of probable rem sleep behavior disorder in parkinson’s disease
publisher MDPI
publishDate 2023
url https://repositorio.uca.edu.ar/handle/123456789/17344
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