Polymorphisms in the SNCA Gene: Association with the Risk of Development of the Sporadic Form of Parkinson’s Disease and the Level of SNCA Gene Expression in Peripheral Blood of Patients from Russia

Anelya Kh Alieva,Elena V Filatova,Petr A Slominsky,Alexey V Karabanov,Vera V Ustinova,Maria I Shadrina,Sergey N Illarioshkin,Ekaterina Yu Fedotova

doi:10.4236/nm.2013.44032

Abstract

Parkinson’s disease (PD) is one of the most common human neurodegenerative disorders caused by the loss of dopaminergic neurons in the brain. The α-synuclein (SNCA) gene is one of the most studied genes involved in the pathogenesis of PD. In our study, we conducted a genetic analysis of promoter and intron single-nucleotide polymorphisms (SNPs) in the SNCA gene. We also analyzed the association of genotypes of these SNPs with expression levels of SNCA mRNA. One of four SNPs in the SNCA gene, and the rs2736990 polymorphism, associates with the risk of the sporadic form of PD in Russian population. The risk of PD was increased almost twofold in carriers of allele C (odds ratios = 1.9, 95% confidence interval: 1.2-2.91, p = 0.003). However, no association was found between any of the genotypes of SNPs tested (rs2583988, rs2619363, rs2619364 and rs2736990) and alterations in SNCA levels. Our findings support the hypothesis that the rs2736990 polymorphism is associated with PD. SNPs rs2583988, rs2619363 and rs2619364 in the promoter region of the SNCA gene themselves do not significantly influence the expression of SNCA. Most likely, SNCA gene expression is a very complex process that is affected by different genetic and epigenetic factors.

Highlights

Parkinson’s disease (PD) is one of the most common human neurodegenerative disorders after Alzheimer’s disease
We analyzed four single-nucleotide polymorphisms (SNPs), three of which were located in the promoter region of the SNCA gene; SNP rs2736990 was located in the fourth intron of the same gene
We investigated whether the relative mRNA levels of the SNCA gene depend on the genotypes of rs2583988, rs2619363, rs2619364 and rs2736990 in patients with PD with early stages of the disorder

Summary

Introduction

Parkinson’s disease (PD) is one of the most common human neurodegenerative disorders after Alzheimer’s disease. SNCA acts as a molecular chaperone and regulates protein-protein interactions in cells [2]. SNCA was the first gene whose association with PD has been shown [6]. The SNCA gene is one of the most studied genes involved in the pathogenesis of PD. Several point mutations in the SNCA gene and duplications and triplications of the genomic region containing SNCA were revealed. They are very rare and lead to the development of an autosomal dominant form of PD [7,8,9,10,11]

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