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Background  The polymorphisms of α-synuclein ( SNCA ), rs3775444, rs3822086 and rs11931074 that are strongly associated with Parkinson’s disease (PD) in Caucasian populations, were examined in this study to elucidate the role of polymorphisms in different ethnic backgrounds. The possible associations of these three polymorphisms were also investigated in PD, amyotrophic lateral sclerosis (ALS), and multiple system atrophy (MSA) in a Chinese population based on the overlapping of clinical manifestations and pathological characteristics of these three neurodegenerative diseases.    Methods  A total of 1276 PD, 885 sporadic ALS (SALS), 364 MSA patients, and 846 healthy controls (HCs) were included. All subjects were genotyped for the three polymorphisms using Sequenom iPLEX Assay technology.    Results  Significant differences in the genotype distributions (p = 5.99E-06 and p = 4.98E-06, respectively) and the minor allele frequency (MAF) (p = 2.16E-06 and p = 2.15E-06, respectively) of  SNCA  rs3822086 (C) and rs11931074 (G) were observed between PD and HCs. However, no differences were found in the genotype distributions and MAF of  SNCA  rs3775444 (T) between PD and HCs. Haplotype that incorporated the three SNPs further strengthened the association with PD (best haplotype, p = 9.62E-005). No significant differences in the genotype distributions and MAF of the SNPs were found between SALS and HCs, MSA and HCs, and subgroups of PD and SALS. However, the MAF of  SNCA  rs3775444 (T) was significantly higher in MSA patients with frontal lobe dysfunction than MSA patients without dysfunction (p = 0.0002, OR 2.53, 95%CI: 1.55-4.15).    Conclusion  Our results suggest that the rs3822086 (C) allele and rs11931074 (G) allele in  SNCA  decrease the risk for PD, and  SNCA  rs11931074 may affect frontal lobe dysfunction of MSA in the Chinese population. However, these  SNCA  polymorphisms are not likely a common cause of SALS or MSA.

plos one

Genetic Variants of SNCA Are Associated with Susceptibility to Parkinson’s Disease but Not Amyotrophic Lateral Sclerosis or Multiple System Atrophy in a Chinese Population