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.
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Acknowledgements
We gratefully acknowledge Sabine Proske-Schmitz and Anne Hanke for technical support. This study was supported in part by the Intramural Bonfor Research Program of the University Bonn (UW), the Hans-Tauber Stiftung of the Deutsche Parkinson Vereinigung (dPV, UW) and the Deutsche Forschungsgemeinschaft (Wu184/9-1).
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Dr. Klein is supported by a career development award from Volkswagen and from the Hermann and Lilly Schilling Foundation. The other authors declare no conflict of interest.
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Schmitt, I., Wüllner, U., van Rooyen, J. et al. Variants in the 3′UTR of SNCA do not affect miRNA-433 binding and alpha-synuclein expression. Eur J Hum Genet 20, 1265–1269 (2012). https://doi.org/10.1038/ejhg.2012.84
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DOI: https://doi.org/10.1038/ejhg.2012.84
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