Li Yuanyuan, Kang Wenyan, Zhang Linyuan, Zhou Liche, Niu Mengyue, Liu Jun
Department of Neurology, Institute of Neurology, Ruijin Hospital Affiliated to School of Medicine, Shanghai Jiaotong UniversityShanghai, China.
Front Aging Neurosci. 2017 Sep 20;9:303. doi: 10.3389/fnagi.2017.00303. eCollection 2017.
Hyposmia may occur simultaneously with REM sleep behavior disorder (RBD) as a specific phenotype in Parkinson's Diseases (PD), of which the disease progression is fast. In the study, we tried to identify whether the genotypic characteristics could participate in the co-occurrence of hyposmia and RBD in PD patients. 152 PD patients were recruited from the Department of Neurology, Ruijin Hospital affiliated to Shanghai JiaoTong University School of Medicine from 2011 to 2016, with comprehensive clinical assessment performing. Two SNPs of (rs11931074 and rs894278) in 105 patients were also analyzed. Overall, 84 of 152 PD patients (55.3%) were diagnosed with RBD after PSG evaluation. After regression analysis, higher levels of three parts of UPDRS and SCOPA-AUT scores were all associated with increased risk of RBD in PD patients, respectively. While for olfactory function, we didn't find significant correlation between hyposmia and RBD in PD patients. However, we found that in the group of minor G allele of rs894278, patients with lower score of SS-16 had a 4.76-fold risk of suffering from RBD in patients (95% CI: 1.39-16.67; = 0.013). Furthermore, we analyzed SNP associated gene expression by eQTL analysis in Genevar database and found that GG genotype of rs894278 was associated with higher levels of α-synuclein in Nerve tissue ( = 1.5E-8) while TT genotype of rs11931074 was associated with higher levels of α-synuclein in Brain ( = 0.0082), which suggesting a potential functional relevance with different symptoms of PD. Hyposmia was associated with RBD in PD patients with the minor G allele of rs894278, which represent one specific subtype of PD. This study could provide more detail information about PD subtype of RBD with hyposmia in the future.
嗅觉减退可能作为帕金森病(PD)的一种特定表型与快速眼动睡眠行为障碍(RBD)同时出现。在本研究中,我们试图确定基因特征是否参与PD患者嗅觉减退和RBD的共同发生。2011年至2016年,从上海交通大学医学院附属瑞金医院神经内科招募了152例PD患者,并进行了全面的临床评估。同时对105例患者的两个单核苷酸多态性(rs11931074和rs894278)进行了分析。总体而言,152例PD患者中有84例(55.3%)经多导睡眠图(PSG)评估后被诊断为RBD。回归分析后,统一帕金森病评定量表(UPDRS)三部分及自主神经症状评分量表(SCOPA-AUT)得分较高均分别与PD患者发生RBD的风险增加相关。而对于嗅觉功能,我们未发现PD患者嗅觉减退与RBD之间存在显著相关性。然而,我们发现,在rs894278的次要G等位基因组中,嗅觉障碍筛查-16项问卷(SS-16)得分较低的患者发生RBD的风险是其他患者的4.76倍(95%置信区间:1.39-16.67;P=0.013)。此外,我们在Genevar数据库中通过表达定量性状位点(eQTL)分析对单核苷酸多态性相关基因表达进行了分析,发现rs894278的GG基因型与神经组织中α-突触核蛋白水平较高相关(P=1.5×10-8),而rs11931074的TT基因型与大脑中α-突触核蛋白水平较高相关(P=0.0082),这表明其与PD的不同症状可能存在潜在的功能相关性。在携带rs894278次要G等位基因的PD患者中,嗅觉减退与RBD相关,这代表了PD的一种特定亚型。本研究未来可为伴有嗅觉减退的RBD的PD亚型提供更详细的信息。