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

摘要

Neurodegeneration in Parkinson’s disease is characterized by theaccumulation of alpha-synuclein, a protein encoded by the gene, in neurons. In addition to mutations, many polymorphisms havebeen identified in this gene, and one of these is a dinucleotidemicrosatellite: -Rep1 The mechanisms bywhich specific configurations of Rep1 may contribute tothe development of this disease have yet to be clarified. In our study, arelationship between long Rep1 alleles andParkinson’s was confirmed in the Russian population. Long allelicvariants of -Rep1 were shown to be associated with thehypomethylation of the CpG-sites in intron 1 of the gene.Long variants of -Rep1 are supposed to exert their effectthrough the hypomethylation of a transcriptionally significant region of thisgene. 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 gene expression.