Category: Parkinson's Disease: Genetics
Objective: Parkinson’s disease (PD) and multiple system atrophy (MSA) are classical synucleinopathies caused by misfolding of alpha-synuclein protein. Clinical picture of PD and MSA in some cases may be very similar, and additional diagnostic methods are needed to distinguish both conditions.
Background: Epigenetic mechanisms, in particular DNA methylation, may play a role in molecular pathogenesis of alpha-synuclein aggregation. Several recent publications showed that methylation level of SNCA gene might be altered in PD patients, but there are no studies on SNCA methylation in MSA patients.
Method: We studied 59 patients with PD (mean age 57.9±9.5 years, 29 males, 30 females) and 22 age- and sex-matched MSA patients (mean age 61,95±9.6 years). We analyzed DNA methylation level in leucocytes by performing bisulfate sequence analysis of intron 1 region of SNCA gene. The selected region contains 28 CpG sites nearby exon 2. In each sample and in each CpG site we calculated a percent of methylation: (C/C+T)*100. The same analysis was also performed in healthy age- and sex-matched control samples (n=26).
Results: In total, 12 of 28 CpG-sites in intron 1 of SNCA gene showed significant hypermethylation in patients with MSA compared to PD patients, and one CpG-site was hypomethylated (p<0.05). In MSA patients compared to control subjects, 8 CpG-sites had higher methylation level, and one CpG was hypomethylated (p<0.05). In the PD group compared to controls, only two sites were significantly hypomethylated (p<0.05). The methylation level did not depend on age or gender.
Conclusion: We present the first data on the analysis of methylation of SNCA in MSA. We suggest that different levels of methylation in PD and MSA groups may be associated with specific patterns of alpha-synuclein deposition in neurons and oligodendroglia and may represent a promising additional diagnostic tool in complicated clinical cases. Further studies are needed to confirm these preliminary results.
To cite this abstract in AMA style:
E. Iakovenko, N. Abramycheva, E. Fedotova, S. Illarioshkin. Methylation status of SNCA gene in multiple system atrophy and Parkinson’s disease [abstract]. Mov Disord. 2021; 36 (suppl 1). https://www.mdsabstracts.org/abstract/methylation-status-of-snca-gene-in-multiple-system-atrophy-and-parkinsons-disease/. Accessed June 15, 2025.« Back to MDS Virtual Congress 2021
MDS Abstracts - https://www.mdsabstracts.org/abstract/methylation-status-of-snca-gene-in-multiple-system-atrophy-and-parkinsons-disease/