Analysis of the Micro-RNA-133 and PITX3 genes in Parkinson's disease

MicroRNAs are small RNA sequences that negatively regulate gene expression by binding to the 3′ untranslated regions of mRNAs. MiR‐133b has been implicated in Parkinson's disease (PD) by a mechanism that involves the regulation of the transcription factor PITX3. The variation in these genes could contribute to the risk of developing PD. We searched for DNA variants in miR‐133 and PITX3 genes in PD patients and healthy controls from Spain. We found common DNA variants in the three miR‐133 genes. Genotyping of a first set of patients (n = 777) and controls (n = 650) showed a higher frequency of homozygous for a miR‐133b variant (−90 del A) in PD‐patients (6/575; 1%) than in healthy controls (0/650) (P = 0.03). However, this association was not confirmed in a second set of patients (1/250; 0.4%) and controls (2/210; 1%). No common PITX3 variants were associated with PD, although a rare missense change (G32S) was found in only one patient and none of the controls. In conclusion, we report the variation in genes of a pathway that has been involved in dopaminergic neuron differentiation and survival. Our work suggests that miR‐133 and PITX3 gene variants did not contribute to the risk for PD. © 2010 Wiley‐Liss, Inc.