The Correlation Between RIN3 Gene Methylation and Cognitive Impairment in Parkinson’s Disease

Background: Parkinson’s disease (PD) is the second most common neurodegenerative disorder, after Alzheimer’s disease. Many individuals with PD experience cognitive impairment, significantly threatening both their physical and mental well-being. Research has shown that abnormal DNA methylation is closely linked to neurodegenerative conditions such as Alzheimer’s and Parkinson’s disease. The RIN3 gene, which encodes a guanine nucleotide exchange factor, plays a role in inhibiting amyloid-beta formation and affects protein endocytosis, both of which are linked to cognitive impairment. However, the potential connection between RIN3 gene methylation and cognitive impairment in Parkinson’s disease has not yet been explored. This study aims to explore whether the methylation status of the RIN3 gene is connected to cognitive decline in Parkinson’s patients, thereby shedding light on the gene’s crucial role in the disease’s development and identifying potential targets for diagnosing and treating cognitive impairment in this context. Purpose: This study aims to explore whether the methylation status of the RIN3 gene is associated with cognitive impairment in Parkinson’s disease and to further clarify the gene’s significant role in the disease’s pathogenesis. Methods: This study involved 50 control subjects and 51 Parkinson’s disease (PD) patients, who were assessed using a cognitive scale. Additionally, DNA methylation in whole blood was analyzed. The research compared RIN3 methylation levels between the PD group and the normal control group (NC), as well as between the subgroups of PD-Mild Cognitive Impairment (PD-MCI), PD-Normal Cognition (PD-NC), and the control group. Results: The DNA methylation level of the RIN3 gene in the whole blood of patients with PD was lower than that in healthy controls (22.3%vs.23.6%, P=0.009). Moreover, individuals with PD-MCI had significantly lower RIN3 methylation levels than both the control group (21.3%vs.23.6%, P<0.001) and those in the PD-NC group (21.3%vs.23.3%, P=0.001). Conclusion: RIN3 methylation is associated with PD-MCI. With appropriate lifestyle changes and clinical interventions, methylation may influence disease progression, suggesting that RIN3 gene methylation could serve as a predictor for the development of PD-MCI.