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

Parkinson's disease (PD) is the second most common neurodegenerative disorder. The presence of Lewy bodies is a major pathological change of PD. alpha-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 alpha-synuclein in extracellular biological fluid are associated with PD and implicated alpha-synuclein as a potential biomarker for PD diagnosis and severity. We studied serum alpha-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 alpha-synuclein. Soluble alpha-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 alpha-synuclein. The frequency of allele T of rs11931074 was significantly elevated in PD patients (p = 0.041), and was correlated with decreased serum alpha-synuclein in both dominant (p = 0.011) and additive (p = 0.008) models of association.