Hypomethylation of SNCA in blood of patients with sporadic Parkinson's disease

Ai, Sanxi; Xu, Qian; Hu, Yacen; Song, Chengyuan; Guo, Jifeng; Shen, Lu; Wang, Chunrong; Yu, Ri-li; Yan, Xinxiang; Tang, Beisha

doi:10.1016/j.jns.2013.11.033

Cited by 90 publications

(80 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Fourteen studies found no difference or clear pattern in methylation of the following genes: 12-LOX [34], debrin-like protein gene [34], p450 epoxygenase gene [34], MAPT , PSEN1 , UCHL1 , SST [52], SSTR4 [52], F2RL2 [45], SOD-1 [48] and GRN [53] in brain tissue; PS1 [49], PS2 [49] and tau1 [49], SMARCA 5 [54], CHD1 [54], BDNF [55], SIRT1 [55], PSEN1 [55{Tannorella, 2015 #2823], genes involved in DNA repair [56], genes involved in homocysteine pathway [57], CTSB [58], CTSD [58], DDT [58], TSC1 [58], NRD1 [58] and NDUFA6 [58] in blood cells; HSPA8 [59], HSPA9 [59], ApoE4 [47, 49], SNAP25 [60], SORL 1 , SIRT1 and SIRT3 [49, 54, 60] in both blood cells and brain tissue (Table 2). However, 7 studies showed differences in methylation patterns of CpG sites (within same gene some CpG sites were hypomethylated and some others were hypermethylated, in AD cases) examined at the following genes: SORL1 [61], ABCA7 [61], SLC2A4 [61], BIN1 [61], HSPA8 [59], HSPA9 [59], DR4 gene [62], BDNF4 [43, 44], SIRT1 [49], APP [47], MAPT [47] and GSK3B [47]. …”

Section: Resultsmentioning

confidence: 99%

“…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%

See 1 more Smart Citation

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

et al. 2016

View full text Add to dashboard Cite

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.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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

et al. 2016

View full text Add to dashboard Cite

show abstract

“…In agreement with the assumption that DNA methylation profiles in the brain could be potentially mirrored in blood cells, a recent study found SNCA promoter hypomethylation in both post-mortem cortex and peripheral blood samples (Pihlstrom et al, 2015). Another study reported hypomethylation of SNCA intron 1 in peripheral blood mononuclear cells of 100 sporadic PD subjects (Ai et al, 2014). In 2015, the largest study carried out to date analyzing 490 peripheral blood samples of patients with sporadic PD, also revealed hypomethylation of SNCA intron 1.…”

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

confidence: 99%

Implications of DNA Methylation in Parkinson’s Disease

Miranda-Morales

Meier

Sandoval-Carrillo

et al. 2017

Front. Mol. Neurosci.

View full text Add to dashboard Cite

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.

show abstract

“…Hundreds of SNPs of SNCA are associated with sporadic PD. In addition, hypomethylation at the promoter and introns of SNCA appear to increase the SNCA expression in PD patients (60, 61). Overexpressed α-Synuclein can also sequester DNMT1 to the cytoplasm; this protein is normally located in the nuclei of neurons in the healthy brain.…”

Section: Epigenetic Changes In Aging-related Neurodegenerative Diseasesmentioning

confidence: 99%

Age-related epigenetic regulation in the brain and its role in neuronal diseases

Kim-Ha¹,

Kim²

2016

BMB Reports

View full text Add to dashboard Cite

Accumulating evidence indicates many brain functions are mediated by epigenetic regulation of neural genes, and their dysregulations result in neuronal disorders. Experiences such as learning and recall, as well as physical exercise, induce neuronal activation through epigenetic modifications and by changing the noncoding RNA profiles. Animal models, brain samples from patients, and the development of diverse analytical methods have broadened our understanding of epigenetic regulation in the brain. Diverse and specific epigenetic changes are suggested to correlate with neuronal development, learning and memory, aging and age-related neuronal diseases. Although the results show some discrepancies, a careful comparison of the data (including methods, regions and conditions examined) would clarify the problems confronted in understanding epigenetic regulation in the brain.

show abstract

Hypomethylation of SNCA in blood of patients with sporadic Parkinson's disease

Cited by 90 publications

References 37 publications

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

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

Implications of DNA Methylation in Parkinson’s Disease

Age-related epigenetic regulation in the brain and its role in neuronal diseases

Contact Info

Product

Resources

About