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.
There is little evidence for the involvement of microRNAs (miRs) in the regulation of circadian rhythms, despite the potential relevance of these elements in the posttranscriptional regulation of the clock machinery. The present work aimed to identify miRs targeting circadian genes through a predictive analysis of conserved miRs in mammals. Besides 23 miRs previously associated with circadian rhythms, we found a number of interesting candidate genes, equally predicted by the 3 software programs used, including miR-9, miR-24, miR25, miR-26, miR-27, miR-29, miR-93, miR-211, miR-302, and miR-346. Moreover, several miRs are predicted to be regulated by circadian transcription factors, such as CLOCK/BMAL, DEC2, and REV-ERBalpha. Using real-time PCR we demonstrated that the selected candidate miR-27b showed a daily variation in human leukocytes. This study presents predicted feedback loops for mammalian molecular clock and the first description of an miR with in vivo daily variation in humans.
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