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在一个巴西样本中,SNCA基因的变异与帕金森病风险及认知症状相关。

Variants in SNCA Gene Are Associated with Parkinson's Disease Risk and Cognitive Symptoms in a Brazilian Sample.

作者信息

Campêlo Clarissa L C, Cagni Fernanda C, de Siqueira Figueredo Diego, Oliveira Luiz G, Silva-Neto Antônio B, Macêdo Priscila T, Santos José R, Izídio Geison S, Ribeiro Alessandra M, de Andrade Tiago G, de Oliveira Godeiro Clécio, Silva Regina H

机构信息

Memory Studies Laboratory, Physiology Department, Universidade Federal do Rio Grande do NorteNatal, Brazil.

Molecular Biology and Gene Expression Laboratory, Universidade Federal de AlagoasArapiraca, Brazil.

出版信息

Front Aging Neurosci. 2017 Jun 20;9:198. doi: 10.3389/fnagi.2017.00198. eCollection 2017.

Abstract

Genetic susceptibility contributes to the etiology of sporadic Parkinson's Disease (PD) and worldwide studies have found positive associations of polymorphisms in the alpha-synuclein gene (SNCA) with the risk for PD. However, little is known about the influence of variants of SNCA in individual traits or phenotypical aspects of PD. Further, there is a lack of studies with Latin-American samples. We evaluated the association between SNCA single nucleotide polymorphisms (single nucleotide polymorphisms, SNPs - rs2583988, rs356219, rs2736990, and rs11931074) and PD risk in a Brazilians sample. In addition, we investigated their potential interactions with environmental factors and specific clinical outcomes (motor and cognitive impairments, depression, and anxiety). A total of 105 PD patients and 101 controls participated in the study. Single locus analysis showed that the risk allele of all SNPs were more frequent in PD patients ( < 0.05), and the associations of SNPs rs2583988, rs356219, and rs2736990 with increased PD risk were confirmed. Further, the G-rs356219 and C-rs2736990 alleles were associated with early onset PD. T-rs2583988, G-rs356219 and C-2736990 alleles were significantly more frequent in PD patients with cognitive impairments than controls in this condition. In addition, in a logistic regression model, we found an association of cognitive impairment with PD, and the practice of cognitive activity and smoking habits had a protective effect. This study shows for the first time an association of SNCA polymorphism and PD in a South-American sample. In addition, we found an interaction between SNP rs356219 and a specific clinical outcome, i.e., the increased risk for cognitive impairment in PD patients.

摘要

遗传易感性对散发性帕金森病(PD)的病因学有影响,全球范围内的研究发现α-突触核蛋白基因(SNCA)多态性与PD风险呈正相关。然而,关于SNCA变异对PD个体特征或表型方面的影响知之甚少。此外,缺乏针对拉丁裔样本的研究。我们评估了SNCA单核苷酸多态性(单核苷酸多态性,SNPs - rs2583988、rs356219、rs2736990和rs11931074)与巴西样本中PD风险之间的关联。此外,我们研究了它们与环境因素和特定临床结局(运动和认知障碍、抑郁和焦虑)的潜在相互作用。共有105名PD患者和101名对照参与了该研究。单基因座分析表明,所有SNPs的风险等位基因在PD患者中更为常见(<0.05),并且SNPs rs2583988、rs356219和rs2736990与PD风险增加之间的关联得到了证实。此外,G-rs356219和C-rs2736990等位基因与早发性PD相关。在这种情况下,T-rs2583988、G-rs356219和C-2736990等位基因在有认知障碍的PD患者中比对照组明显更常见。此外,在逻辑回归模型中,我们发现认知障碍与PD之间存在关联,并且认知活动和吸烟习惯的行为具有保护作用。这项研究首次表明南美样本中SNCA多态性与PD之间存在关联。此外,我们发现SNP rs356219与特定临床结局之间存在相互作用,即PD患者认知障碍风险增加。

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