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

Abstract

Neurodegeneration in Parkinsons disease is characterized by the accumulation of alpha-synuclein, aprotein encoded by theSNCAgene, in neurons. In addition to mutations, many polymorphisms have been identified in this gene, and one of theseis a dinucleotide microsatellite:SNCA-Rep1.The mechanisms by which specific configurations ofSNCA-Rep1 may contribute to the development of this disease have yet to be clarified. Inour study, a relationship between longSNCA-Rep1 alleles and Parkinsons was confirmed in the Russian population. Long allelic variants ofSNCA-Rep1 were shown to be associated with the hypomethylation of the CpG-sites in intron 1 of theSNCAgene. Long variants ofSNCA-Rep1 are supposed to exert their effect through the hypomethylation of atranscriptionally 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 Parkinsons disease. Further studies are needed to establish a relationship between our finding andSNCAgene expression.

The Impact of SNCA Variations and Its Product Alpha-Synuclein on Non-Motor Features of Parkinson’s Disease

“…Authors found a significant correlation between intron 1 site methylation and Rep1 allele length, with longer alleles correlating with hypomethylations. In contrast, no correlations were detected with promoter sites and in controls [ 57 ].…”