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

被引：8

作者：

Li, Yuan ^{[1
,2
]}

Hao, Shuwen ^{[2
,3
]}

Zhang, Hui ^{[1
,2
]}

Mao, Wei ^{[1
]}

Xue, Jinhua ^{[2
,3
]}

Zhang, Yanli ^{[2
,3
]}

Cai, Yanning ^{[2
,3
,4
]}

Chan, Piu ^{[1
,2
,3
,5
]}

机构：

[1] Capital Med Univ, Xuanwu Hosp, Dept Neurol, Beijing, Peoples R China

[2] Capital Med Univ, Xuanwu Hosp, Dept Neurobiol, Beijing, Peoples R China

[3] Capital Med Univ, Clin & Res Ctr Parkinsons Dis, Beijing Inst Brain Disorders,Key Lab Neurodegener, Parkinsons Dis Ctr,Minist Educ,Beijing Key Lab Pa, Beijing, Peoples R China

[4] Capital Med Univ, Xuanwu Hosp, Dept Biobank, Beijing, Peoples R China

[5] Natl Clin Res Ctr Geriatr Disorders, Beijing, Peoples R China

来源：

MOVEMENT DISORDERS | 2021年 / 36卷 / 04期

基金：

中国国家自然科学基金; 国家重点研发计划;

关键词：

DNA methylation; SNCA; idiopathic REM sleep behavior disorder; phenoconversion; ALPHA-SYNUCLEIN; DNA METHYLATION; PROMOTER METHYLATION; CONSENSUS STATEMENT; ALZHEIMERS-DISEASE; LEUKOCYTE DNA; BLOOD; IDENTIFICATION; EXPRESSION; DIAGNOSIS;

D O I：

10.1002/mds.28421

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

Background Hypomethylation of intron 1 of the alpha-synuclein (SNCA) gene has been extensively reported in the blood of patients with alpha-synucleinopathies. Idiopathic rapid eye movement sleep behavior disorder represents a prodromal stage of alpha-synucleinopathies. Methylation of alpha-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 alpha-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 alpha-synuclein intron 1 was hypomethylated in idiopathic rapid eye movement sleep behavior disorder patients. alpha-Synuclein methylation levels may be useful biomarkers to screen patients, predict phenoconversion, and monitor disease progression. (c) 2020 International Parkinson and Movement Disorder Society

引用

页码：955 / 962

页数：8

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