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: | , , , , , , |
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| Formato: | Artículo |
| Lenguaje: | Inglés |
| Publicado: |
MDPI
2023
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| Materias: | |
| Acceso en línea: | https://repositorio.uca.edu.ar/handle/123456789/17344 |
| Aporte de: |
| Sumario: | 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. |
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