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Neurodegeneration in Parkinson's disease is characterized by the accumulation of alpha-synuclein, a protein encoded by the SNCA gene, in neurons. In addition to mutations, many polymorphisms have been identified in this gene, and one of these is a dinucleotide microsatellite: SNCA -Rep1 . The mechanisms by which specific configurations of SNCA- Rep1 may contribute to the development of this disease have yet to be clarified. In our study, a relationship between long SNCA- Rep1 alleles and Parkinson's was confirmed in the Russian population. Long allelic variants of SNCA -Rep1 were shown to be associated with the hypomethylation of the CpG-sites in intron 1 of the SNCA gene. Long variants of SNCA -Rep1 are supposed to exert their effect through the hypomethylation of a transcriptionally significant region of this gene. Hypomethylation is usually associated with increased expression, which, in turn, contributes to alpha-synuclein accumulation in neuronal cytoplasm, with the latter being the main molecular marker of Parkinson's disease. Further studies are needed to establish a relationship between our finding and SNCA gene expression.

The SNCA-Rep1 Polymorphic Locus: Association with the Risk of Parkinson’s Disease and SNCA Gene Methylation