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Hypomethylation of SNCA in Idiopathic REM Sleep Behavior Disorder Associated With Phenoconversion.
Mov Disord. 2021 04; 36(4):955-962.MD

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.

Authors+Show Affiliations

Department of Neurology, Xuanwu Hospital of Capital Medical University, Beijing, China. Department of Neurobiology, Xuanwu Hospital of Capital Medical University, Beijing, China.Department of Neurobiology, Xuanwu Hospital of Capital Medical University, Beijing, China. Key Laboratory for Neurodegenerative Diseases of the Ministry of Education, Beijing Key Laboratory on Parkinson's Disease, Parkinson's Disease Center for Beijing Institute on Brain Disorders, Clinical and Research Center for Parkinson's Disease of Capital Medical University, Beijing, China.Department of Neurology, Xuanwu Hospital of Capital Medical University, Beijing, China. Department of Neurobiology, Xuanwu Hospital of Capital Medical University, Beijing, China.Department of Neurology, Xuanwu Hospital of Capital Medical University, Beijing, China.Department of Neurobiology, Xuanwu Hospital of Capital Medical University, Beijing, China. Key Laboratory for Neurodegenerative Diseases of the Ministry of Education, Beijing Key Laboratory on Parkinson's Disease, Parkinson's Disease Center for Beijing Institute on Brain Disorders, Clinical and Research Center for Parkinson's Disease of Capital Medical University, Beijing, China.Department of Neurobiology, Xuanwu Hospital of Capital Medical University, Beijing, China. Key Laboratory for Neurodegenerative Diseases of the Ministry of Education, Beijing Key Laboratory on Parkinson's Disease, Parkinson's Disease Center for Beijing Institute on Brain Disorders, Clinical and Research Center for Parkinson's Disease of Capital Medical University, Beijing, China.Department of Neurobiology, Xuanwu Hospital of Capital Medical University, Beijing, China. Key Laboratory for Neurodegenerative Diseases of the Ministry of Education, Beijing Key Laboratory on Parkinson's Disease, Parkinson's Disease Center for Beijing Institute on Brain Disorders, Clinical and Research Center for Parkinson's Disease of Capital Medical University, Beijing, China. Department of Biobank, Xuanwu Hospital of Capital Medical University, Beijing, China.Department of Neurology, Xuanwu Hospital of Capital Medical University, Beijing, China. Department of Neurobiology, Xuanwu Hospital of Capital Medical University, Beijing, China. Key Laboratory for Neurodegenerative Diseases of the Ministry of Education, Beijing Key Laboratory on Parkinson's Disease, Parkinson's Disease Center for Beijing Institute on Brain Disorders, Clinical and Research Center for Parkinson's Disease of Capital Medical University, Beijing, China. National Clinical Research Center for Geriatric Disorders, Beijing, China.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

33340152

Citation

Li, Yuan, et al. "Hypomethylation of SNCA in Idiopathic REM Sleep Behavior Disorder Associated With Phenoconversion." Movement Disorders : Official Journal of the Movement Disorder Society, vol. 36, no. 4, 2021, pp. 955-962.
Li Y, Hao S, Zhang H, et al. Hypomethylation of SNCA in Idiopathic REM Sleep Behavior Disorder Associated With Phenoconversion. Mov Disord. 2021;36(4):955-962.
Li, Y., Hao, S., Zhang, H., Mao, W., Xue, J., Zhang, Y., Cai, Y., & Chan, P. (2021). Hypomethylation of SNCA in Idiopathic REM Sleep Behavior Disorder Associated With Phenoconversion. Movement Disorders : Official Journal of the Movement Disorder Society, 36(4), 955-962. https://doi.org/10.1002/mds.28421
Li Y, et al. Hypomethylation of SNCA in Idiopathic REM Sleep Behavior Disorder Associated With Phenoconversion. Mov Disord. 2021;36(4):955-962. PubMed PMID: 33340152.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Hypomethylation of SNCA in Idiopathic REM Sleep Behavior Disorder Associated With Phenoconversion. AU - Li,Yuan, AU - Hao,Shuwen, AU - Zhang,Hui, AU - Mao,Wei, AU - Xue,Jinhua, AU - Zhang,Yanli, AU - Cai,Yanning, AU - Chan,Piu, Y1 - 2020/12/19/ PY - 2020/10/21/revised PY - 2020/07/17/received PY - 2020/11/20/accepted PY - 2020/12/20/pubmed PY - 2021/5/20/medline PY - 2020/12/19/entrez KW - DNA methylation KW - SNCA KW - idiopathic REM sleep behavior disorder KW - phenoconversion SP - 955 EP - 962 JF - Movement disorders : official journal of the Movement Disorder Society JO - Mov Disord VL - 36 IS - 4 N2 - 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. SN - 1531-8257 UR - https://www.unboundmedicine.com/medline/citation/33340152/Hypomethylation_of_SNCA_in_Idiopathic_REM_Sleep_Behavior_Disorder_Associated_With_Phenoconversion_ L2 - https://doi.org/10.1002/mds.28421 DB - PRIME DP - Unbound Medicine ER -