SNCA rs3910105 Is Associated With Development of Rapid Eye Movement Sleep Behavior Disorder in Parkinson’s Disease

Background and PurposeRapid eye movement (REM) Rapid eye movement sleep behavior disorder (RBD) is a common non-motor symptom of PD. However, the association between the SNCA rs3910105 genotype and RBD in Parkinson’s disease (PD) remains unclear.MethodsThis study used Parkinson’s Progression Markers Initiative (PPMI) data and included 270 patients with newly diagnosed PD without RBD who were divided into SNCA rs3910105 C carriers (CC+CT; n = 187) and TT carriers (n = 83). They were followed up for 5 years to identify the development of RBD. To investigate the influence of cerebrospinal fluid (CSF) alpha-synuclein (α-syn) and β-amyloid 1–42 (Aβ42) in the association between rs3910105 and RBD, the patients were additionally classified into “high-level” and “low-level” groups using cutoff values for CSF α-syn and Aβ42 levels.ResultsAt baseline, the rs3910105 C allele group had lower CSF α-syn and Aβ42 levels than the TT group. During the 5.0-year follow-up, the rs3910105 C allele group had a higher incidence of RBD than the TT group. In the subgroup analyses, the effect of the rs3910105 C allele was not found in the “low-level” group. However, in the “high-level” group, the rs3910105 C allele independently increased the risk of RBD.ConclusionThe SNCA rs3910105 C allele might be a novel genetic risk factor for RBD development in PD, α-syn pathways might have a role in this association and more basic research would be needed to elucidate the mechanism in the future.