title: Variants in the 3'UTR of SNCA do not affect miRNA-433 binding and alpha-synuclein expression.
abstract: 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.
authors.affiliation: Department of Neurology, University of Bonn, Bonn, Germany.
authors.forename: Ina
authors.initials: I
authors.lastname: Schmitt
authors.forename: Ullrich
authors.initials: U
authors.lastname: Wüllner
authors.forename: Jan Pierre
authors.initials: JP
authors.lastname: van Rooyen
authors.forename: Hassan
authors.initials: H
authors.lastname: Khazneh
authors.forename: Julian
authors.initials: J
authors.lastname: Becker
authors.forename: Alexander
authors.initials: A
authors.lastname: Volk
authors.forename: Christian
authors.initials: C
authors.lastname: Kubisch
authors.forename: Tim
authors.initials: T
authors.lastname: Becker
authors.forename: Vladimir S
authors.initials: VS
authors.lastname: Kostic
authors.forename: Christine
authors.initials: C
authors.lastname: Klein
authors.forename: Alfredo
authors.initials: A
authors.lastname: Ramirez
mesh_terms: D020413:3' Untranslated Regions; D000328:Adult; D000368:Aged; D000483:Alleles; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D008875:Middle Aged; D010300:Parkinson Disease / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D014158:Transcription, Genetic; D051844:alpha-Synuclein / Q000235:genetics* / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; C548883:MIRN433 microRNA, human; D035683:MicroRNAs; C497604:SNCA protein, human; D051844:alpha-Synuclein