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RIN3基因甲基化与帕金森病认知障碍之间的相关性

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

作者信息

Yu Xiaolong, Zhu Konghua, Wang Tingting, Li Hai Yan, Zhang Xue, Zhong Xiaoling, Wang Ling

机构信息

Department of Neurology, Qingdao Central Hospital, University of Health and Rehabilitation Sciences (Qingdao Central Medical Group), Qingdao, Shandong, People's Republic of China.

Department of Neurology, Qingdao Eighth People's Hospital, Qingdao, Shandong, People's Republic of China.

出版信息

Neuropsychiatr Dis Treat. 2025 Mar 7;21:511-524. doi: 10.2147/NDT.S509510. eCollection 2025.

Abstract

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.

摘要

背景

帕金森病(PD)是仅次于阿尔茨海默病的第二常见神经退行性疾病。许多帕金森病患者会出现认知障碍,这对他们的身心健康构成了重大威胁。研究表明,异常的DNA甲基化与阿尔茨海默病和帕金森病等神经退行性疾病密切相关。编码鸟嘌呤核苷酸交换因子的RIN3基因在抑制β-淀粉样蛋白形成中起作用,并影响蛋白质内吞作用,这两者都与认知障碍有关。然而,RIN3基因甲基化与帕金森病认知障碍之间的潜在联系尚未得到探索。本研究旨在探讨RIN3基因的甲基化状态是否与帕金森病患者的认知衰退有关,从而揭示该基因在疾病发展中的关键作用,并确定在这种情况下诊断和治疗认知障碍的潜在靶点。

目的

本研究旨在探讨RIN3基因的甲基化状态是否与帕金森病的认知障碍相关,并进一步阐明该基因在疾病发病机制中的重要作用。

方法

本研究纳入了50名对照受试者和51名帕金森病(PD)患者,使用认知量表对他们进行评估。此外,还分析了全血中的DNA甲基化情况。研究比较了PD组与正常对照组(NC)之间以及PD-轻度认知障碍(PD-MCI)、PD-正常认知(PD-NC)亚组与对照组之间的RIN3甲基化水平。

结果

PD患者全血中RIN3基因的DNA甲基化水平低于健康对照组(22.3%对23.6%,P = 0.009)。此外,PD-MCI患者的RIN3甲基化水平显著低于对照组(21.3%对23.6%,P < 0.001)和PD-NC组患者(21.3%对23.3%,P = 0.001)。

结论

RIN3甲基化与PD-MCI相关。通过适当的生活方式改变和临床干预,甲基化可能会影响疾病进展,这表明RIN3基因甲基化可作为PD-MCI发生发展的预测指标。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b763/11900794/971b47bd5d32/NDT-21-511-g0001.jpg

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