SNCA Variants and Expression Levels of α-synuclein Transcripts in Multiple System Atrophy: A Retrospective Case–control Study. / Zhuravlev, Alexandr; Lavrinova, Anna ; Pidyurchina, Victoria; Demidova, Evgeniya; Фаюд, Хайдар; Timofeeva, Alla; Miliukhina, Irina; Pchelina, Sofya; Emelyanov, Anton.
In: Gene Expression, Vol. 25, No. 2, 20.04.2026.Research output: Contribution to journal › Article › peer-review
}
TY - JOUR
T1 - SNCA Variants and Expression Levels of α-synuclein Transcripts in Multiple System Atrophy: A Retrospective Case–control Study
AU - Zhuravlev, Alexandr
AU - Lavrinova, Anna
AU - Pidyurchina, Victoria
AU - Demidova, Evgeniya
AU - Фаюд, Хайдар
AU - Timofeeva, Alla
AU - Miliukhina, Irina
AU - Pchelina, Sofya
AU - Emelyanov, Anton
PY - 2026/4/20
Y1 - 2026/4/20
N2 - Background and objectives: Synucleinopathies, including Parkinson’s disease (PD), dementia with Lewy bodies, and multiple system atrophy (MSA), are a group of neurodegenerative diseases characterized by the oligomerization of α-synuclein protein in neurons or glial cells. Various splicing isoforms of α-synuclein have been described, each with different aggregation properties. The α-synuclein gene (SNCA) has been identified as a highly significant genetic risk locus associated with various synucleinopathies across populations. This study aimed to assess the association of SNCA genetic variants with MSA and the levels of SNCA transcripts in peripheral blood mononuclear cells (PBMCs) from MSA and PD patients. Methods: In this retrospective case–control study, 96 MSA patients, 1086 PD patients, and 485 healthy volunteers were included. PCR followed by restriction endonuclease analysis was used to detect four SNCA single-nucleotide polymorphisms (rs356219, rs3756063, rs11931074, and rs356168) in these individuals. In addition, RT-qPCR was performed to detect the levels of α-synuclein transcripts (SNCA mRNA isoforms -140, -126, and -112) in PBMCs of 24 MSA patients (including parkinsonian (MSA-P) and cerebellar (MSA-C) variants), 31 PD patients, and 32 healthy volunteers. Results: The frequency of the ‘T’ allele (of rs11931074) was significantly higher in MSA patients than in the healthy controls. The level of SNCA-140 mRNA was significantly decreased in MSA and PD patients compared with the controls, while the level of SNCA-112 mRNA was significantly increased in MSA-P patients than in PD patients and the controls. SNCA-112 mRNA/SNCA-140 mRNA and SNCA-112 mRNA/SNCA-126 mRNA ratios were significantly increased in MSA patients than in the controls. Conclusions: The SNCA rs11931074 polymorphism is associated with MSA. There is a pronounced alteration in the expression of SNCA transcripts in PBMCs of MSA and PD patients.
AB - Background and objectives: Synucleinopathies, including Parkinson’s disease (PD), dementia with Lewy bodies, and multiple system atrophy (MSA), are a group of neurodegenerative diseases characterized by the oligomerization of α-synuclein protein in neurons or glial cells. Various splicing isoforms of α-synuclein have been described, each with different aggregation properties. The α-synuclein gene (SNCA) has been identified as a highly significant genetic risk locus associated with various synucleinopathies across populations. This study aimed to assess the association of SNCA genetic variants with MSA and the levels of SNCA transcripts in peripheral blood mononuclear cells (PBMCs) from MSA and PD patients. Methods: In this retrospective case–control study, 96 MSA patients, 1086 PD patients, and 485 healthy volunteers were included. PCR followed by restriction endonuclease analysis was used to detect four SNCA single-nucleotide polymorphisms (rs356219, rs3756063, rs11931074, and rs356168) in these individuals. In addition, RT-qPCR was performed to detect the levels of α-synuclein transcripts (SNCA mRNA isoforms -140, -126, and -112) in PBMCs of 24 MSA patients (including parkinsonian (MSA-P) and cerebellar (MSA-C) variants), 31 PD patients, and 32 healthy volunteers. Results: The frequency of the ‘T’ allele (of rs11931074) was significantly higher in MSA patients than in the healthy controls. The level of SNCA-140 mRNA was significantly decreased in MSA and PD patients compared with the controls, while the level of SNCA-112 mRNA was significantly increased in MSA-P patients than in PD patients and the controls. SNCA-112 mRNA/SNCA-140 mRNA and SNCA-112 mRNA/SNCA-126 mRNA ratios were significantly increased in MSA patients than in the controls. Conclusions: The SNCA rs11931074 polymorphism is associated with MSA. There is a pronounced alteration in the expression of SNCA transcripts in PBMCs of MSA and PD patients.
KW - Multiple system atrophy
KW - Parkinson’s disease
KW - SNCA expression
KW - SNCA single-nucleotide polymorphisms
KW - SNCA transcripts
KW - α-synuclein
UR - https://www.mendeley.com/catalogue/69db9efe-ba80-3bb5-bb14-f2e635133655/
U2 - 10.14218/GE.2025.00091
DO - 10.14218/GE.2025.00091
M3 - Article
VL - 25
JO - Gene Expression
JF - Gene Expression
SN - 1052-2166
IS - 2
ER -
ID: 157209571