Variants in the 3'UTR of SNCA do not affect miRNA-433 binding and alpha-synuclein expression

Eur J Hum Genet. 2012 Dec;20(12):1265-9. doi: 10.1038/ejhg.2012.84. Epub 2012 May 23.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions*
  • Adult
  • Aged
  • Alleles
  • Case-Control Studies
  • Female
  • Humans
  • Male
  • MicroRNAs / metabolism*
  • Middle Aged
  • Parkinson Disease / genetics*
  • Polymorphism, Single Nucleotide*
  • Transcription, Genetic*
  • alpha-Synuclein / genetics*
  • alpha-Synuclein / metabolism

Substances

  • 3' Untranslated Regions
  • MIRN433 microRNA, human
  • MicroRNAs
  • SNCA protein, human
  • alpha-Synuclein