Bjørnarå Kari Anne, Pihlstrøm Lasse, Dietrichs Espen, Toft Mathias
Department of Neurology, Drammen Hospital, Vestre Viken Hospital Trust, Dronninggata 21, 3004, Drammen, Norway.
Department of Neurology, Oslo University Hospital, Oslo, Norway.
BMC Neurol. 2018 Feb 21;18(1):20. doi: 10.1186/s12883-018-1023-6.
Parkinson's disease is a heterogeneous disorder where genetic factors may underlie clinical variability. Rapid eye movement sleep behavior disorder (RBD) is a parasomnia strongly linked to synucleinopathies, including Parkinson's disease. We hypothesized that SNCA variants conferring risk of Parkinson's disease would also predispose to an RBD phenotype.
We assessed possible RBD (pRBD) status using the RBD screening questionnaire and investigated known susceptibility variants for Parkinson's disease located in the α-synuclein (SNCA) and tau (MAPT) gene loci in 325 Parkinson's disease patients. Associations between genetic risk variants and RBD were investigated by logistic regression, and an independent dataset of 382 patients from the Parkinson's Progression Marker Initiative (PPMI) study was used for replication.
pRBD was associated with rs3756063 located in the 5' region of SNCA (two-sided p = 0.018, odds ratio 1.44). We replicated this finding in the PPMI dataset (one-sided p = 0.036, odds ratio 1.35) and meta-analyzed the results (two-sided p = 0.0032, odds ratio 1.40). The Parkinson's disease risk variant in the 3' region of SNCA and the MAPT variant showed no association with pRBD.
Our findings provide proof of principle that a largely stable, dichotomous clinical feature of Parkinson's disease can be linked to a specific genetic susceptibility profile. Indirectly, it also supports the hypothesis of RBD as relevant marker for a distinct subtype of the disorder.
帕金森病是一种异质性疾病，其中遗传因素可能是临床变异性的基础。快速眼动睡眠行为障碍（RBD）是一种与包括帕金森病在内的突触核蛋白病密切相关的异态睡眠。我们假设，赋予帕金森病风险的SNCA变异也会使个体易患RBD表型。
我们使用RBD筛查问卷评估可能的RBD（pRBD）状态，并在325例帕金森病患者中研究位于α-突触核蛋白（SNCA）和微管相关蛋白tau（MAPT）基因座的已知帕金森病易感性变异。通过逻辑回归研究遗传风险变异与RBD之间的关联，并使用来自帕金森病进展标记物倡议（PPMI）研究的382例患者的独立数据集进行重复验证。
pRBD与位于SNCA 5'区域的rs3756063相关（双侧p = 0.018，比值比1.44）。我们在PPMI数据集中重复了这一发现（单侧p = 0.036，比值比1.35），并对结果进行了荟萃分析（双侧p = 0.0032，比值比1.40）。SNCA 3'区域的帕金森病风险变异和MAPT变异与pRBD无关联。
我们的研究结果提供了原理证明，即帕金森病一个基本稳定的二分临床特征可与特定的遗传易感性特征相关联。间接而言，这也支持了RBD作为该疾病一种独特亚型的相关标志物的假说。
