Variant in the 3′ region of SNCA associated with Parkinson’s disease and serum α-synuclein levels

• Published in: Journal of neurology Vol. 259; no. 3; pp. 497 - 504
• Main Authors: Hu, Yacen, Tang, Beisha, Guo, Jifeng, Wu, Xintian, Sun, Qiying, Shi, Changhe, Hu, Liang, Wang, Chunyu, Wang, Lei, Tan, Liming, Shen, Lu, Yan, Xinxiang, Zhang, Hainan
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer-Verlag 01.03.2012; Springer
• Subjects: 3' Untranslated Regions - genetics; Adult; Aged; alpha-Synuclein - blood; alpha-Synuclein - genetics; Biological and medical sciences; biomarkers; Case-Control Studies; Chi-Square Distribution; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Female; Gene Frequency; Gene polymorphism; Genetic Predisposition to Disease; Genotype; Humans; Lewy bodies; Lewy Bodies - pathology; Male; Medical sciences; Medicine; Medicine & Public Health; Middle Aged; Movement disorders; Mutation; Mutation - genetics; Neurodegenerative diseases; Neurology; Neuroradiology; Neurosciences; Original Communication; Parkinson's disease; Parkinsonian Disorders - blood; Parkinsonian Disorders - genetics; Statistical analysis; Statistics, Nonparametric; Synuclein; rs11931074; Rep1; Parkinson’s disease; Serum α-synuclein; SNCA; Polymorphism; Nervous system diseases; Parkinson's disease; Central nervous system disease; Parkinson disease; Repl; Degenerative disease; Cerebral disorder; Extrapyramidal syndrome
• ISSN: 0340-5354; 1432-1459; 1432-1459
• DOI: 10.1007/s00415-011-6209-4

Parkinson’s disease (PD) is the second most common neurodegenerative disorder. The presence of Lewy bodies is a major pathological change of PD. α-synuclein is the main component of Lewy bodies and is encoded by the SNCA gene. Mutations in the SNCA gene mainly result in rare familial forms of PD, while genetic variability in the SNCA gene modulates susceptibility to sporadic PD. Recent studies have suggested that levels of α-synuclein in extracellular biological fluid are associated with PD and implicated α-synuclein as a potential biomarker for PD diagnosis and severity. We studied serum α-synuclein concentration and two polymorphic variants of SNCA (Rep1 and rs11931074) in 110 sporadic PD patients and 136 controls. We further explored the influence of the two polymorphisms on the expression levels of serum α-synuclein. Soluble α-synuclein was detected in serum in all subjects, with no statistically significant difference between PD patients and controls ( p  = 0.611). Different Rep1 alleles and genotypes did not influence the expression of serum α-synuclein. The frequency of allele T of rs11931074 was significantly elevated in PD patients ( p  = 0.041), and was correlated with decreased serum α-synuclein in both dominant ( p  = 0.011) and additive ( p  = 0.008) models of association.