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Variants in the 3'UTR of SNCA do not affect miRNA-433 binding and alpha-synuclein expression.
MedLine Citation:
PMID:  22617348     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Alpha-synuclein (SNCA) is a major risk gene for Parkinson's disease (PD) and increased SNCA gene dosage results in a parkinsonian syndrome in affected families. Regulatory regions relevant for SNCA expression include the 3' untranslated region (UTR), which among other regulatory elements contains several micro-RNA-binding sites. Interestingly, variants located in the 3' region of SNCA have been associated with PD in two genome-wide association studies. To test whether private mutations in this region contribute to PD, we sequenced the 3'UTR of SNCA in 1285 PD patients and 1120 age/sex-matched healthy controls. We found two rare variants, the one corresponding to the single nucleotide polymorphism rs145304567 and the novel variant c.*1004_1008delTTTTT. Although rs145304567 affects the putative-binding site of microRNA (miRNA) -433, the allele distribution was similar in PD patients and controls, and the expression of SNCA mRNA was not related to the genotype. Furthermore, a regulatory effect of miRNA-433 on SNCA expression levels was not detected.European Journal of Human Genetics advance online publication, 23 May 2012; doi:10.1038/ejhg.2012.84.
Authors:
Ina Schmitt; Ullrich Wüllner; Jan Pierre van Rooyen; Hassan Khazneh; Julian Becker; Alexander Volk; Christian Kubisch; Tim Becker; Vladimir S Kostic; Christine Klein; Alfredo Ramirez
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-5-23
Journal Detail:
Title:  European journal of human genetics : EJHG     Volume:  -     ISSN:  1476-5438     ISO Abbreviation:  -     Publication Date:  2012 May 
Date Detail:
Created Date:  2012-5-23     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9302235     Medline TA:  Eur J Hum Genet     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
1] Department of Neurology, University of Bonn, Bonn, Germany [2] German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.
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