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Analysis of the Micro-RNA-133 and PITX3 genes in Parkinson's disease
Lorena de Mena1, Eliecer Coto, Lucía F Cardo
1Genética Molecular, Hospital Universitario Central de Asturias, Oviedo, Spain.
Abstract:
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.
Insights
Genetic variations in miR-133b and PITX3 were investigated for Parkinson's disease (PD) risk. While an initial hint of association was found for a miR-133b variant, further analysis did not confirm its role in PD development.
Area of Science:
- Neurogenetics
- Molecular Biology
- Gene Regulation
Background:
- MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression.
- MiR-133b is involved in Parkinson's disease (PD) pathogenesis through PITX3 regulation.
- Genetic variations in miRNA and transcription factor genes may influence PD susceptibility.
Purpose of the Study:
- To investigate the association between genetic variants in miR-133 and PITX3 genes and the risk of developing Parkinson's disease.
- To analyze DNA variations in Spanish PD patients and healthy controls.
Main Methods:
- Genotyping of common DNA variants in miR-133 and PITX3 genes.
- Case-control study design with two independent sets of Spanish participants.
- Statistical analysis to compare variant frequencies between PD patients and controls.
Main Results:
- Common variants were identified in the miR-133 genes.
- An initial association of a miR-133b variant (-90 del A) with PD was observed in the first cohort (P=0.03) but not replicated in the second cohort.
- No significant association was found for common PITX3 variants; a rare variant (G32S) was found in one patient only.
Conclusions:
- Genetic variations in miR-133 and PITX3 do not appear to be significant risk factors for Parkinson's disease in the studied Spanish population.
- The investigated pathway involving miR-133 and PITX3 in dopaminergic neuron survival may not be a major contributor to PD risk through common genetic variations.
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