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A diagnostic model for Parkinson’s disease based on circadian rhythm-related genes

作者:Lufeng Wang, Yiwen Bao, Xiaofan Duan, Hongxia Li, Hao Ding, Fei Yu, Jie Yang, Yongbo Hu, Dongya Huang · 发表于:Journal of Translational Medicine · 年份:2024 · DOI:10.1186/s12967-024-05424-z · 被引用次数:8 · 研究领域:Parkinson's Disease Mechanisms and Treatments、Circadian rhythm and melatonin、Sleep and related disorders

BACKGROUND: Circadian rhythm (CR) disturbance is intricately associated with Parkinson's disease (PD). However, the involvement of CR-related mechanisms in the pathogenesis and progression of PD remains elusive. METHODS: A total of 141 PD patients and 113 healthy participants completed CR-related clinical examinations in this study. To further investigate the CR-related mechanisms in PD, we obtained datasets (GSE7621, GSE20141, GSE20292) from the Gene Expression Omnibus database to identify differentially expressed genes between PD patients and healthy controls and further selected CR-related genes (CRRGs). Subsequently, the least absolute shrinkage and selection operator (LASSO) followed by logistic algorithms were employed to identify the hub genes and construct a diagnostic model. The predictive performance was evaluated by area under the curve (AUC), calibration curve, and decision curve analyses in the training set and external validation sets. Finally, RT‒qPCR and Western blotting were conducted to verify the expression of these hub genes in blood samples. In addition, Pearson correlation analysis was utilized to validate the association between expression of hub genes and circadian rhythm function. RESULTS: Our clinical observational study revealed that even early-stage PD patients exhibited a higher likelihood of experiencing sleep disturbances, nocturnal hypertension, reverse-dipper blood pressure, and reduced heart rate variability compared to healthy controls. Furt...