Expression of the gene coading for PGC-1α in peripheral blood leukocytes and related gene variants in patients with Parkinson's disease.

Introduction: Peroxisome proliferator-activated receptor (PPAR)-γ coactivator-1α (PGC-1α) plays an important role in Parkinson's disease (PD). The aim of the study was to evaluate PGC-1α gene expression in the peripheral blood of PD patients. We also investigated PGC-1α-related gene variants and identified whether they are associated with PGC-1α gene expression.

Methods: 259 PD patients and 253 healthy controls were included in this study. PPARGC1A (the gene encoding PGC-1α) expression levels were tested using real-time PCR. Single nucleotide polymorphisms (SNPs) of the PGC-1α-related genes (PPARGC1A, PPARG and SIRT1) were genotyped by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS).

Results: PPARGC1A levels were significantly decreased in PD patients (P = 0.000) and negatively correlated with the patients' H&Y stage (r = -0.212, P = 0.039) and UPDRS-III score (r = -0.208, P = 0.044), after correcting, these correlations disappeared. The genotype frequencies of PGC-1α-related gene variants were not associated with the risk of PD. PPARGC1A rs2970870 variant was associated with the NMS score (P = 0.026), SIRT1 rs7895833 variant was associated with HAMA score (P = 0.029). PPARG rs4684847 variant was associated with MMSE score (P = 0.031). PPARG rs1801282, rs4684847, rs3856806 variants were associated with MoCA score. After correcting, only the association between PPARG rs4684847 and MoCA score remained significant (FDR = 0.048). PGC-1α-related gene variants had no effect on PGC-1α gene expression.

Conclusion: The decreased expression of PGC-1α may not be due to its related gene variants. PGC-1α could become a candidate blood-based biomarker for diagnosis and monitoring disease progression.