A single nucleotide polymorphism in the 3′UTR of the SNCA gene encoding alpha-synuclein is a new potential susceptibility locus for Parkinson disease

Sotiriou, Sotiria; Gibney, Gretchen; Baxevanis, Andreas D.; Nussbaum, Robert L.

doi:10.1016/j.neulet.2009.06.034

Cited by 61 publications

(72 citation statements)

References 27 publications

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“…A logistic regression analysis using the allele dosage of the most associated SNP in each block as a covariate, did not change the results observed at the most associated signal in the other, indicating that the two signals are independent (Supplementary Table 2) and being in disagreement with previous results. 7,25,32 LD analysis between these two SNPs revealed a r 2 value of 0.028 and a D' value of 0.388, further supporting this hypothesis.…”

Section: Sncasupporting

confidence: 58%

“…[6][7][8][25][26][27][28][29][30][31][32] The data presented here supports the hypothesis that two different signals in these blocks are present in the Dutch population, which is in controversy with previous results. 7,28,[30][31][32] In a report by Mueller et al, 25 the authors also detected two association signals in the 3¢ and 5¢ blocks of SNCA. Interestingly, when stratifying their cohort into males and females, as well as young and old PD groups (according to the median age of 57 years), additional significant association in the intron 4 region of the 5¢ block was found for the female and the young patients' subgroups.…”

Section: Discussionsupporting

confidence: 42%

“…[6][7][8][25][26][27][28][29][30][31][32] In an effort to delineate the signal at this locus, we examined the LD structure across this region. This analysis revealed two LD blocks delimited at the intron 4 of SNCA as previously described [6][7][8]25 (Supplementary Figure 4).…”

Section: Sncamentioning

confidence: 99%

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Genome-wide association study confirms extant PD risk loci among the Dutch

et al. 2011

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Section: Sncasupporting

confidence: 58%

Section: Discussionsupporting

confidence: 42%

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Genome-wide association study confirms extant PD risk loci among the Dutch

et al. 2011

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“…Increasing evidence suggests that dysregulated miRNAs directly contribute to the pathogenesis of a variety of human diseases [30][31][32][33][34]. SNPs in miRNA target sites in the 3' UTR of mRNAs are referred to as polymorphisms in microRNAs and their target sites (polymiRTSs) and can affect mRNA half-life, resulting in decreased protein levels due to mRNAmiRNA interactions and increased susceptibility to many diseases [30-33, 35, 36], including PD [33].…”

Section: Discussionmentioning

confidence: 99%

miR-486-3p Influences the Neurotoxicity of a-Synuclein by Targeting the SIRT2 Gene and the Polymorphisms at Target Sites Contributing to Parkinson’s Disease

Wang

Cai

Huang

et al. 2018

Cell Physiol Biochem

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Background/Aims: Increasing evidence suggests the important role of sirtuin 2 (SIRT2) in the pathology of Parkinson’s disease (PD). However, the association between potential functional polymorphisms in the SIRT2 gene and PD still needs to be identified. Exploring the molecular mechanism underlying this potential association could also provide novel insights into the pathogenesis of this disorder. Methods: Bioinformatics analysis and screening were first performed to find potential microRNAs (miRNAs) that could target the SIRT2 gene, and molecular biology experiments were carried out to further identify the regulation between miRNA and SIRT2 and characterize the pivotal role of miRNA in PD models. Moreover, a clinical case-control study was performed with 304 PD patients and 312 healthy controls from the Chinese Han population to identify the possible association of single nucleotide polymorphisms (SNPs) within the miRNA binding sites of SIRT2 with the risk of PD. Results: Here, we demonstrate that miR-486-3p binds to the 3’ UTR of SIRT2 and influences the translation of SIRT2. MiR-486-3p mimics can decrease the level of SIRT2 and reduce a-synuclein (α-syn)-induced aggregation and toxicity, which may contribute to the progression of PD. Interestingly, we find that a SNP, rs2241703, may disrupt miR-486-3p binding sites in the 3’ UTR of SIRT2, subsequently influencing the translation of SIRT2. Through the clinical case-control study, we further verify that rs2241703 is associated with PD risk in the Chinese Han population. Conclusion: The present study confirms that the rs2241703 polymorphism in the SIRT2 gene is associated with PD in the Chinese Han population, provides the potential mechanism of the susceptibility locus in determining PD risk and reveals a potential target of miRNA for the treatment and prevention of PD.

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“…The 3'-UTR of SNCA is highly conserved across species (Sotiriou et al, 2009) and few of the SNPs identified in this region exhibit sufficient heterozygosity for further study. However, alcohol-use phenotypes have been associated with SNCA 3'-UTR polymorphisms.…”

Section: Introductionmentioning

confidence: 99%

Differential expression of α-synuclein splice variants in the brain of alcohol misusers: Influence of genotype

Janeczek

Brooker

Dodd

et al. 2015

Drug and Alcohol Dependence

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Please cite this article as: Janeczek, P., Brooker, C., Lewohl, P.D.,J.M., Differential Expression of rmalpha-Synuclein Splice Variants in the Brain of Alcohol Misusers: Influence of Genotype, Drug and Alcohol Dependence (2015), http://dx.doi.org/10. 1016/j.drugalcdep.2015.05.045 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Allele and genotype frequencies differed significantly between alcohol misusers and controls for three SNPs, rs356221, rs356219 and rs2736995. Two SNPs, rs356221 and rs356219, were in high linkage disequilibrium. There was no increased risk of alcoholism associated with specific genotypes or haplotypes. Our results suggest that the rs356219/356221 G-A haplotype may decrease the chance of having an alcohol misuse phenotype. Conclusion: These findings suggest that alcohol misuse may alter the expression of the individual α-synuclein splice variants differently in human brain. There was no evidence of an effect of sequence variation on the expression of α-synuclein splice variants in this population.

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A single nucleotide polymorphism in the 3′UTR of the SNCA gene encoding alpha-synuclein is a new potential susceptibility locus for Parkinson disease

Cited by 61 publications

References 27 publications

Genome-wide association study confirms extant PD risk loci among the Dutch

Genome-wide association study confirms extant PD risk loci among the Dutch

miR-486-3p Influences the Neurotoxicity of a-Synuclein by Targeting the SIRT2 Gene and the Polymorphisms at Target Sites Contributing to Parkinson’s Disease

Differential expression of α-synuclein splice variants in the brain of alcohol misusers: Influence of genotype

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