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
Memory Studies Laboratory, Physiology Department, Universidade Federal do Rio Grande do NorteNatal, Brazil.
Molecular Biology and Gene Expression Laboratory, Universidade Federal de AlagoasArapiraca, Brazil.
Front Aging Neurosci. 2017 Jun 20;9:198. doi: 10.3389/fnagi.2017.00198. eCollection 2017.
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.
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。