Objective: To assess the impact of twenty-one single nucleotide polymorphisms (SNPs) located in different regulatory regions of the SNCA gene on the risk of developing multiple system atrophy (MSA) in a cohort of patients from the Russian population.To assess the impact of twenty-one single nucleotide polymorphisms (SNPs) located in different regulatory regions of the SNCA gene on the risk of developing multiple system atrophy (MSA) in a cohort of patients from the Russian population.
Background: Most forms of synucleinopathies are sporadic and have a multifactorial nature, which determines the involvement of various risk factors in their development. One of these predisposing genetic factors is the influence of polymorphic variants of the SNCA gene.
Method: The study included 115 patients: 50 diagnosed with MSA and 65 individuals in the control group. Genotyping of SNCA SNPs was performed using Sanger sequencing on a capillary genetic analyzer. Statistical analysis was performed using SPSS Statistics 26.0 (IBM SPSS), also we interpreted the results using the Benjamini-Hochberg correction for multiple comparisons.
Results: Twelve of the 21 analyzed polymorphic variants of the SNCA gene turned out to be statistically significant for risk (padj<0.05) and a quantitative assessment of the relationship between the presence of the disease and the status of the genotype was carried out for them. Eight analyzed SNPs (rs7687945, rs2301134, rs2301135, rs3756063, rs2736990, rs3822086, rs3857059, rs11931074) showed a significant association with the risk of developing MSA, four more SNPs (rs2619361, rs2619362, rs2619363, and rs2619364) showed the protective role of the minor allele. Also we explored the contributions of heterozygotes and homozygotes concerning each variant using dominant and recessive models. Almost all the SNPs have confirmed their role in increasing or reducing risk only in the dominant inheritance model. rs2736990 has not demonstrated risk in any of the hereditary models.
Conclusion: Thus, our study identified significant associations of SNCA polymorphisms with the risk of developing multiple system atrophy. This work requires further continuation in larger, well-characterized patient cohorts as part of comprehensive studies on the role of SNCA gene.
The study was conducted as part of the RSF grant No. 24-25-00478 “Implementation of genetic and epigenetic predisposition to synucleinopathies.”
To cite this abstract in AMA style:
N. Abramycheva, M. Andreev, L. Karan, I. Minaev, A. Protopopova, A. Protsenko, E. Fedotova, S. Illaroshkin. Analysis of the Association between SNCA Polymorphisms and the Risk of Multiple System Atrophy [abstract]. Mov Disord. 2025; 40 (suppl 1). https://www.mdsabstracts.org/abstract/analysis-of-the-association-between-snca-polymorphisms-and-the-risk-of-multiple-system-atrophy/. Accessed October 5, 2025.« Back to 2025 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/analysis-of-the-association-between-snca-polymorphisms-and-the-risk-of-multiple-system-atrophy/