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

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 (p < 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.

Motor Complications in Parkinson's Disease: 13‐Year Follow‐up of the CamPaIGN Cohort

“…Association of the SNCA rs356219 A allele and MF is an unexpected finding because this variant has been associated with reduced PD susceptibility and older age at onset, [29][30][31] as well as reduced plasma α-synuclein levels in PD. 32 Our observed association may reflect less severe diffuse α-synuclein pathology in levodoparesponsive patients who develop early MF, but it is a finding that requires further replication in an independent cohort.…”

SNCAandmTORPathway Single Nucleotide Polymorphisms Interact to Modulate the Age at Onset of Parkinson's Disease

“…Yet single nucleotide polymorphisms (SNPs) in the SNCA and the microtubule‐associated protein Tau ( MAPT ) genes have shown top‐hit association signals with PD risk in genomewide association studies and in candidate gene studies . For instance, the SNP rs356219 in the 3’ untranslated region (3’‐UTR) of SNCA is a haplotype‐tag SNP associated with a higher risk of PD and related to increased SNCA protein expression . This tag SNP also modulates AAO in both IPD and leucine‐rich repeat kinase 2 (LRRK2)–associated PD (L2PD) .…”

The Relationship between Alpha-Synuclein (SNCA) Gene Polymorphisms and Development Risk of Parkinson’s Disease

“…Parkinson's disease (PD), the second most common neurodegenerative disease after Alzheimer's disease, affects approximately 1-2% of individuals over 65 years of age [11,12]. The incidence of PD usually begins after 50 years of age and increases more after 60 years of age [13]. The prevalence of PD increases approximately 4% in people over 85 years of age [6].…”

“…In a study conducted in the United States, it was found that some single-nucleotide gene polymorphisms in the SNCA gene were associated with the risk of PD development, but no significant relationship was determined between rs11931074 gene polymorphism and PD development risk [46]. In a study conducted with a South American Brazilian population, the relationship between rs2583988, rs356219, rs2736990, and rs11931074 gene polymorphisms and the risk of PD development was investigated, and the significant relationship was determined between rs356219 gene polymorphism and increased cognitive disorder in PD patients [13]. In studies conducted with European and North American populations, rs2736990 gene polymorphism has been identified as a genetic risk factor in PD development [47].…”

“…Tyrosine hydroxylase activity and dopamine release decrease as a result of SNCA overexpression. In order to investigate the relationship between SNCA gene polymorphisms and the risk of PD development, different results have been obtained in studies performed with different populations [13].…”