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.
| Original language | English |
|---|---|
| Journal | European Journal of Human Genetics |
| Volume | 20 |
| Issue number | 12 |
| Pages (from-to) | 1265-1269 |
| Number of pages | 5 |
| ISSN | 1018-4813 |
| DOIs | |
| Publication status | Published - 01.12.2012 |
Funding
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. 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).
