rs2737029

This meta-analysis of 19 studies (comprising 31 case-control studies) examined 10 SNCA gene polymorphisms and Parkinson's disease (PD) risk. Eight SNPs showed significant associations with PD: rs181489 (OR 1.678, Caucasian), rs356186 (protective, OR 0.653, Caucasian), rs356219 (OR 1.523, Caucasian), rs894278 (OR 1.493, Asian), rs2583988 (OR 1.409, Caucasian), rs2619364 (OR 1.346, Caucasian), rs10005233 (OR 1.359 in dominant model, Caucasian), and rs11931074 (OR 1.798 overall). Two SNPs (rs2619363 and rs2737029) showed no significant association. Results indicate SNCA is a common susceptibility marker for PD in both Asian and Caucasian populations.

This case-control association study of 1,956 Parkinson's disease (PD) patients and 2,112 controls identified rs356219 (OR=1.41, 95% CI 1.28-1.55, p=1.6×10⁻¹²) as a major genetic susceptibility variant for PD located ~9 kb downstream of SNCA. The risk allele was associated with increased plasma α-synuclein levels in PD cases (p=0.005), suggesting the functional variant tagged by rs356219 may upregulate SNCA expression in a dose-dependent manner, independent of the previously known REP1 promoter repeat polymorphism.