DNA Methylation of the SNCA Intron 1 and Alpha-Synuclein Expression in the CD45+ Blood Cells in Parkinson's Disease.

Alpha-synuclein oligomers are believed to be the major neurotoxic agents in neurodegenerative process in Parkinson's disease (PD). The SNCA gene expression has been shown to be regulated by methylation of the SNCA intron 1. Polymorphisms in the SNCA promoter and 3'-untranslated regions could affect the SNCA gene expression and gene methylation. The study included 46 L-DOPA-naïve sporadic PD (sPD) patients and 64 individuals in the control group. We evaluated methylation of the SNCA intron 1 in the CD45+ blood cells along with the SNCA expression (mRNA, protein) in the sPD patients and controls. Negative correlations were found between the levels of DNA methylation of all of 23 CpG sites and of individual CpG sites in the SNCA intron 1 and the levels of alpha-synuclein expression (mRNA and protein) in the controls. No difference in the methylation of the SNCA intron 1 in the CD45+ blood cells between the PD patients and controls was found. However, hypermethylation of the CpG site at position 22 in the intron 1 of the SNCA gene in the sPD patients was revealed. It was found that the rs3756063 SNCA genotype influence the SNCA intron 1 methylation level in the CD45+ blood cells both in the sPD patients and controls. Influence of the rs3756063 SNCA genotypes on the alpha-synuclein levels in the CD45+ blood cells was found in the group of sPD patients. Therefore, our data demonstrated that methylation of the SNCA intron 1 is associated with the alpha-synuclein expression levels in the CD45+ blood cells in the controls, but methylation status does not differ between the sPD patients and controls. The obtained results confirmed the effect of rs3756063 polymorphism on methylation of the SNCA intron 1 in the CD45+ blood cells.