Pyrosequencing analysis of SNCA methylation levels in leukocytes from Parkinson's disease patients

Yang, Song; Ding, Hui; Yang, Jiao; Lin, Qingling; Xue, Jinhua; Zhang, Yanli; Chan, Piu; Cai, Yanning

doi:10.1016/j.neulet.2014.03.076

Cited by 45 publications

(40 citation statements)

References 17 publications

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“…While increased methylation of cytosine usually retards the binding of the transcriptional machinery in the promoter region and suppresses the transcription and expression of target genes, series of evidences indicate that decreased cytosine methylation in the promoter region is substantially associated with the facilitated expression of target gene. A significant hypomethylation in the CpG sites in promoter region of Snca was recently reported in the leukocytes (Tan et al, 2014) and postmortem brain samples (Desplats et al, 2011;Matsumoto et al, 2010) in the patients with sporadic PD, while debates remained (Song et al, 2014). Hence, it was postulated that the significantly decreased cytosine methylation in Snca promoter region largely underlay the upregulation of α-synuclein in the substantia nigra in the rats exposed to METH.…”

Section: Discussionmentioning

confidence: 92%

Epigenetic upregulation of alpha-synuclein in the rats exposed to methamphetamine

Jiang

Zhang

et al. 2014

European Journal of Pharmacology

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Section: Discussionmentioning

confidence: 92%

Epigenetic upregulation of alpha-synuclein in the rats exposed to methamphetamine

Jiang

Zhang

et al. 2014

European Journal of Pharmacology

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“…Overall the studies looking at PD found lower levels of methylation of NAPS2 and NOS2 in blood cells and of ADORA2A in the brain tissue of PD cases, and higher levels of methylation of PGC−1α gene in brain tissue of PD patients. Six studies examined the methylation pattern of α-synuclein gene ( SNCA ) in blood and brain tissue in relation to PD: 5 studies [19, 62–65] showed significantly decreased levels of methylation in PD patients compared to controls whereas 1 study [66] found a non-significant decrease in PD subjects. Four studies [53, 67–69] did not show any difference in DNA methylation of the following genes: Parkin gene, DJ-1 , PER1 , PER2 , CRY1 , CRY2 , CLOCK and BMAL1 in blood cells and of GRN in brain tissue.…”

Section: Resultsmentioning

confidence: 99%

The Role of DNA Methylation and Histone Modifications in Neurodegenerative Diseases: A Systematic Review

et al. 2016

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ImportanceEpigenetic modifications of the genome, such as DNA methylation and histone modifications, have been reported to play a role in neurodegenerative diseases (ND) such as Alzheimer’s disease (AD) and Parkinson’s disease (PD).ObjectiveTo systematically review studies investigating epigenetic marks in AD or PD.MethodsEleven bibliographic databases (Embase.com, Medline (Ovid), Web-of-Science, Scopus, PubMed, Cinahl (EBSCOhost), Cochrane Central, ProQuest, Lilacs, Scielo and Google Scholar) were searched until July 11th 2016 to identify relevant articles. We included all randomized controlled trials, cohort, case-control and cross-sectional studies in humans that examined associations between epigenetic marks and ND. Two independent reviewers, with a third reviewer available for disagreements, performed the abstract and full text selection. Data was extracted using a pre-designed data collection form.ResultsOf 6,927 searched references, 73 unique case-control studies met our inclusion criteria. Overall, 11,453 individuals were included in this systematic review (2,640 AD and 2,368 PD outcomes). There was no consistent association between global DNA methylation pattern and any ND. Studies reported epigenetic regulation of 31 genes (including cell communication, apoptosis, and neurogenesis genes in blood and brain tissue) in relation to AD and PD. Methylation at the BDNF, SORBS3 and APP genes in AD were the most consistently reported associations. Methylation of α-synuclein gene (SNCA) was also found to be associated with PD. Seven studies reported histone protein alterations in AD and PD.ConclusionMany studies have investigated epigenetics and ND. Further research should include larger cohort or longitudinal studies, in order to identify clinically significant epigenetic changes. Identifying relevant epigenetic changes could lead to interventional strategies in ND.

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“…Another recent study found no intron 1 hypomethylation of SNCA in a limited number of PD patients (Guhathakurta et al, 2017). Moreover, the analysis of blood samples from 43 PD subjects provided no evidence for DNA methylation changes within the SNCA promoter region (Richter et al, 2012), just as another study comprising blood leukocyte samples of 50 PD patients (Song et al, 2014). However, it should be noted, that in the latter two studies (Richter et al, 2012; Song et al, 2014) 10 times less subjects participated compared to the analysis of Schmitt et al (2015) that detected differential DNA methylation at the SNCA gene.…”

Section: Dna Methylation and Pd: Analysis Of The Snca Genementioning

confidence: 98%

Implications of DNA Methylation in Parkinson’s Disease

Miranda-Morales

Meier

Sandoval-Carrillo

et al. 2017

Front. Mol. Neurosci.

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It has been 200 years since Parkinson’s disease (PD) was first described, yet many aspects of its etiopathogenesis remain unclear. PD is a progressive and complex neurodegenerative disorder caused by genetic and environmental factors including aging, nutrition, pesticides and exposure to heavy metals. DNA methylation may be altered in response to some of these factors; therefore, it is proposed that epigenetic mechanisms, particularly DNA methylation, can have a fundamental role in gene–environment interactions that are related with PD. Epigenetic changes in PD-associated genes are now widely studied in different populations, to discover the mechanisms that contribute to disease development and identify novel biomarkers for early diagnosis and future pharmacological treatment. While initial studies sought to find associations between promoter DNA methylation and the regulation of associated genes in PD brain tissue, more recent studies have described concordant DNA methylation patterns between blood and brain tissue DNA. These data justify the use of peripheral blood samples instead of brain tissue for epigenetic studies. Here, we summarize the current data about DNA methylation changes in PD and discuss the potential of DNA methylation as a potential biomarker for PD. Additionally, we discuss environmental and nutritional factors that have been implicated in DNA methylation. Although the search for significant DNA methylation changes and gene expression analyses of PD-associated genes have yielded inconsistent and contradictory results, epigenetic modifications remain under investigation for their potential to reveal the link between environmental risk factors and the development of PD.

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Pyrosequencing analysis of SNCA methylation levels in leukocytes from Parkinson's disease patients

Cited by 45 publications

References 17 publications

Epigenetic upregulation of alpha-synuclein in the rats exposed to methamphetamine

Epigenetic upregulation of alpha-synuclein in the rats exposed to methamphetamine

The Role of DNA Methylation and Histone Modifications in Neurodegenerative Diseases: A Systematic Review

Implications of DNA Methylation in Parkinson’s Disease

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