Department of Neurology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
Institute of Medical Biometry and Statistics, University of Luebeck, Germany.
Parkinsonism Relat Disord. 2019 Apr;61:151-155. doi: 10.1016/j.parkreldis.2018.10.028. Epub 2018 Oct 26.
Alpha-synuclein (α-Syn) immunostaining in the enteric nervous system (ENS) has been investigated to determine the role of diagnostic biomarker of Parkinson's disease (PD). However, determining factors for alpha-synuclein (α-Syn) deposition in the ENS of humans are still unclear. We aimed to investigate a possible association between SNCA variants and the presence of α-Syn immunostaining in the ENS in patients with PD and healthy individuals.
The study subjects consisted of 38 patients with PD and 46 healthy individuals. α-Syn immunohistochemistry was performed for gastric and colonic mucosal tissues of patients with PD and controls. Mucosal biopsy tissues of the ENS were obtained using standard biopsy forceps by endoscopic gastroduodenoscopy or colonoscopy. Two variants within the SNCA gene (the single nucleotide polymorphism [SNP] rs11931074 and the microsatellite REP1) were genotyped.
In patients with PD, the rs11931074 (G allele) was significantly associated with the presence of α-Syn immunostaining in the ENS (OR = 5.96, 95% CI = 1.70-20.97, P = 0.01). In an interaction analysis, SNP rs11931074-PD status interaction was significantly associated with positive α-Syn immunostaining in the ENS (OR = 7.33, 95% CI = 1.58-33.88, P = 0.01). Longer SNCA REP1 alleles were not associated with positive α-Syn immunostaining in the ENS.
This exploratory study demonstrated that α-Syn deposition in the ENS may be associated with SNCA variants in patients with PD.
α-突触核蛋白（α-Syn）在肠神经系统（ENS）中的免疫染色已被研究，以确定其是否为帕金森病（PD）的诊断生物标志物。然而，人类 ENS 中α-突触核蛋白（α-Syn）沉积的决定因素仍不清楚。我们旨在研究 SNCA 变体与 PD 患者和健康个体 ENS 中α-Syn 免疫染色之间可能存在的关联。
研究对象包括 38 名 PD 患者和 46 名健康个体。对 PD 患者和对照组的胃和结肠黏膜组织进行α-Syn 免疫组织化学染色。通过内镜胃十二指肠镜或结肠镜检查，使用标准活检钳从 ENS 黏膜活检组织中获得。对 SNCA 基因中的两个变体（单核苷酸多态性 [SNP] rs11931074 和微卫星 REP1）进行基因分型。
在 PD 患者中，rs11931074（G 等位基因）与 ENS 中α-Syn 免疫染色的存在显著相关（OR=5.96，95%CI=1.70-20.97，P=0.01）。在交互分析中，SNP rs11931074-PD 状态交互作用与 ENS 中阳性α-Syn 免疫染色显著相关（OR=7.33，95%CI=1.58-33.88，P=0.01）。较长的 SNCA REP1 等位基因与 ENS 中阳性α-Syn 免疫染色无关。
这项探索性研究表明，PD 患者 ENS 中α-Syn 的沉积可能与 SNCA 变体有关。
