Polymorphisms in the <i>SNCA</i> gene and the risk of synucleopathy

Introduction. Synucleinopathies are mostly sporadic and multifactorial neurodegenerative disorders, which determines the involvement of various risk factors in their development. The polymorphic variants of the SNCA gene are considered as one of the predisposing genetic factors. Study aim: to evaluate the effect of the 16 single nucleotide polymorphisms (SNP) located in various regulatory regions of the SNCA gene on the risk of developing three main forms of synucleinopathy — PD, DBL, and MSA — in Russian cohort of patients. Materials and methods. The study included 73 PD patients, 46 MSA patients, 10 DLB patients, and 62 healthy volunteers. Genotyping of 16 SNPs of the SNCA gene was performed by direct Sanger sequencing on a capillary genetic analyzer. The Benjamini–Hochberg procedure was applied for multiple pairwise comparisons. Results. A comparative case-control study showed that only one (rs11931074) of the 16 SNP analyzed was associated with PD: the minor T allele, located in the 3’-UTR region of the SNCA gene, increased the risk of PD (OR = 5.19; p 0.05 (Benjamini–Hochberg adjusted p = 0.6)). An association with MSA was found for 11 of 16 SNP. The minor allele of 5 SNP (rs2619364, rs2619363, rs2619362, rs2619361, rs181489) reduced the risk of the disease, while for 6 SNP (rs7687945, rs2301134, rs2301135, rs3756063, rs2736990, rs11931074) increased the risk. The Benjamini–Hochberg procedure neutralized the significance of only one of these associations (rs181489). Conclusion. This study is the first to genotype a large group of polymorphisms located in various regulatory regions of the SNCA gene and to establish significant associations with the risk of developing one of the forms of synucleinopathies, MSA, in the Russian population.