Association of SNCA variants with α-synuclein of gastric and colonic mucosa in Parkinson's disease
Association of SNCA variants with α-synuclein of gastric and colonic mucosa in Parkinson's disease
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DOI：
10.1016/j.parkreldis.2018.10.028
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发表时间：
2019-04-01
影响因子：
4.1
通讯作者：
Klein, Christine
中科院分区：
文献类型：
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作者：
Chung, Sun Ju;Koenig, Inke R.;Klein, Christine
背景：研究了α -突触核蛋白（α -syn）免疫染色在肠神经系统（ENS）中的作用，以确定帕金森病（PD）的诊断生物标志物。然而，人类ENS中α -突触核蛋白（α -syn）沉积的决定因素尚不清楚。我们的目的是研究SNCA变异与PD患者和健康人ENS中α - syn免疫染色之间的可能关联。方法：研究对象为38例PD患者和46例健康人。对PD患者和对照组的胃和结肠粘膜组织进行α - syn免疫组化。内镜下胃十二指肠镜或结肠镜下，使用标准活检钳获得ENS粘膜活检组织。对SNCA基因内的两个变异（单核苷酸多态性rs11931074和微卫星REP1）进行了基因分型。结果：在PD患者中，rs11931074 （G等位基因）与ENS中α - syn免疫染色存在显著相关（OR = 5.96, 95% CI = 1.70 ~ 20.97, P = 0.01）。在相互作用分析中，SNP rs11931074 PD状态相互作用与ENS中α - syn免疫染色阳性显著相关（OR = 7.33, 95% CI = 1.58-33.88, P = 0.01）。较长的SNCA REP1等位基因与ENS中α - syn阳性免疫染色无关。结论：本探索性研究表明，ENS中α - syn沉积可能与PD患者的SNCA变异有关。
Background: Alpha-synuclein (alpha-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 (alpha-Syn) deposition in the ENS of humans are still unclear. We aimed to investigate a possible association between SNCA variants and the presence of alpha-Syn immunostaining in the ENS in patients with PD and healthy individuals.Methods: The study subjects consisted of 38 patients with PD and 46 healthy individuals. alpha-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.Results: In patients with PD, the rs11931074 (G allele) was significantly associated with the presence of alpha-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 alpha-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 alpha-Syn immunostaining in the ENS.Conclusion: This exploratory study demonstrated that alpha-Syn deposition in the ENS may be associated with SNCA variants in patients with PD.