Association of synuclein alpha (SNCA) gene polymorphisms with spontaneous brain activity in patients with Parkinson’s disease

Background: The synuclein alpha (SNCA) gene responsible for encoding alpha-synuclein, is believed to play a crucial role in the pathogenesis of Parkinson's disease (PD). However, the specific impact of SNCA gene single-nucleotide polymorphisms (SNPs) on brain function in PD remains unclear. Therefore, this cross-sectional retrospective study, particularly through use of imaging analysis, aimed to characterize the relationship between SNCA gene SNPs and spontaneous brain activity in PD in order to enhance our understanding of the mechanisms underlying PD pathogenesis. Methods: A total of 63 patients with PD and 73 sex- and age-matched healthy control (HC) participants were recruited from outpatient and inpatient clinics at Fujian Medical University Union Hospital from August 2017 to November 2019, and all underwent a resting-state functional magnetic resonance imaging (rs-fMRI) scanning. All participants were also examined to determine the correlation of different genotypes with regional brain activity measured by rs-fMRI using amplitude of low-frequency fluctuation (ALFF) analysis. Multivariate regression analysis was used to calculate the correlation between the brain function data and clinical features. All rs-fMRI data were analyzed with the SPM12 software and adjusted according to the false discovery rate (FDR) at the cluster level. Results: This study included 63 patients with PD and 73 sex- and age-matched healthy participants were included in the study. The spontaneous brain activity in the right superior cerebellum (CerebelumCrus1R), vermis (Vermis₇), and left supplementary motor area (SuppMotorAreaL) of patients in the PD group was weak compared to that in the HC group. The z-score ALFF of left central posterior gyrus was positively correlated with the Mini-Mental State Examination score (r=0. 542; P<0. 001) in the PD group. For rs11931074, the main genotypic effects were found in the left inferior cerebellum (Cerebellum₉L) and right anterior cingulate and paracingulate gyri (CingulumAntR) ; for rs356219 and rs356165, the main genotypic effects were found in the left caudate nucleus (CaudateL). An interaction effect of disease with genotype was found in the right inferior parietal gyrus (ParietalInfR) only for rs356219. Conclusions: Our study found a correlation of the SNCA SNPs rs11931074, rs356219, and rs356165 with brain functional alterations in patients with PD. Furthermore, an interaction effect was found in the right inferior parietal gyrus only for rs356219. This study may contribute to furthering the understanding of the influence of SNCA gene SNPs on brain function in patients with PD.