SNCA alleles rs356219 and rs356165 are associated with Parkinson’s disease and increased α-synuclein gene expression in CD45+ blood cells

Impaired metabolism of α-synuclein (SNCA) and its aggregation are key molecular events underlying Parkinson’s disease (PD). Emerging data show that there is a connection between PD and the gene locus containing the SNCA gene. Meta-analyses have demonstrated a highly significant PD connection with single nucleotide polymorphisms (SNPs) rs356165 (A/G) and rs356219 (A/G) in the SNCA gene. We conducted SNP genotyping in 260 PD patients ( n = 260) and 262 healthy people ( n = 262) from northwestern regions of Russia. Linkage disequilibrium was registered between rs356219 and rs356165 alleles (D' = 0.926). It was confirmed that G alleles (rs356165 and rs356219) are associated with increased risk of PD development. For the first time, we have evaluated the relationship between rs356165 and rs356219 and levels of SNCA mRNA and α-synuclein protein in CD45 + peripheral blood cells in drug-naïve PD patients ( n = 43) and controls ( n = 39). Both the level of mRNA SNCA gene and that of α-synuclein protein were increased in carriers of rs356219 and rs356165 compared to carriers with AA genotype in control group (in the group of healthy people) ( p = 0.046 and p = 0.039, respectively). Linkage disequilibrium was shown between associated marker alleles. Our data suggest that rs356165 and rs356219 allele variants may affect the PD development by up-regulation of SNCA expression.