特发性 REM 睡眠行为障碍与表型转化相关的 SNCA 低甲基化。

Hypomethylation of SNCA in Idiopathic REM Sleep Behavior Disorder Associated With Phenoconversion.

机构信息

Department of Neurology, Xuanwu Hospital of Capital Medical University, Beijing, China.

Department of Neurobiology, Xuanwu Hospital of Capital Medical University, Beijing, China.

出版信息

Mov Disord. 2021 Apr;36(4):955-962. doi: 10.1002/mds.28421. Epub 2020 Dec 19.

DOI:10.1002/mds.28421

PMID:33340152

Abstract

BACKGROUND

Hypomethylation of intron 1 of the α-synuclein (SNCA) gene has been extensively reported in the blood of patients with α-synucleinopathies. Idiopathic rapid eye movement sleep behavior disorder represents a prodromal stage of α-synucleinopathies. Methylation of α-synuclein intron 1 in idiopathic rapid eye movement sleep behavior disorder patients is largely unexplored. The objective of the current study was to assess blood α-synuclein intron 1 methylation in patients and to explore it as a potential biomarker to predict phenoconversion and monitor disease progression.

METHODS

Seventy-eight polysomnography-confirmed patients and 74 healthy controls were enrolled. After an average of 3.75 years of follow up, 16 patients converted to neurodegenerative diseases (converters), whereas 59 did not (nonconverters). Blood DNA was obtained at baseline from all participants, as well as at the follow-up visit for 27 patients. DNA methylation levels were determined using bisulfite pyrosequencing methods and were compared between patients and healthy controls, converters and nonconverters, and baseline and follow-up visits.

RESULTS

Hypomethylation at cytosine-phosphate-guanine 10, 11, 12, 13, and 17 was found in patients compared with healthy controls. Hypomethylation at cytosine-phosphate-guanine 17 was associated with an increased risk of clinical phenoconversion, which was further enhanced with the presence of subtle motor abnormalities. In addition, it appeared that later reduction in methylation levels at cytosine-phosphate-guanine 14, 15, and 16 was associated with disease progression.

CONCLUSIONS

Peripheral blood α-synuclein intron 1 was hypomethylated in idiopathic rapid eye movement sleep behavior disorder patients. α-Synuclein methylation levels may be useful biomarkers to screen patients, predict phenoconversion, and monitor disease progression. © 2020 International Parkinson and Movement Disorder Society.

摘要

背景

α-突触核蛋白（SNCA）基因内含子 1 的低甲基化在 α-突触核蛋白病患者的血液中被广泛报道。特发性快速眼动睡眠行为障碍代表了 α-突触核蛋白病的前驱阶段。特发性快速眼动睡眠行为障碍患者的α-突触核蛋白内含子 1 的甲基化在很大程度上尚未被探索。本研究的目的是评估患者血液中α-突触核蛋白内含子 1 的甲基化，并将其作为潜在的生物标志物来预测表型转化和监测疾病进展。

方法

纳入了 78 例经多导睡眠图确诊的患者和 74 例健康对照者。平均随访 3.75 年后，16 例患者转化为神经退行性疾病（转化者），而 59 例未转化（非转化者）。所有参与者均在基线时以及 27 例患者的随访时获得了血液 DNA。采用亚硫酸氢盐焦磷酸测序方法测定 DNA 甲基化水平，并比较了患者与健康对照者、转化者与非转化者以及基线与随访时的水平。