Hypermethylation of the Gene Coding for PGC-1α in Peripheral Blood Leukocytes of Patients With Parkinson’s Disease

Decreased expression of peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) is implicated in the pathophysiology of Parkinson’s disease (PD). However, our understanding of the mechanism of regulating PGC-1α expression is still limited. We sought to determine whether epigenetic modification of PPARGC1A (the gene encoding PGC-1α) could account for its diminished expression. We performed a study of PPARGC1A risk-SNP genotypes, methylation level, and expression in blood from 171 subjects. The mean DNA methylation level of PPARGC1A intron 1 in patients with PD was higher than that in controls (7. 18 ± 1. 74 vs. 6. 36 ± 1. 28, P = 0. 007). A detailed comparison of DNA methylation level at each CpG site showed that CpG₁, CpG₁3. 14, CpG₁7. 18 and CpG₂0 were significantly hypermethylated in patients with PD. There was a significant negative correlation between PPARGC1A methylation and expression level (R = -0. 404, P < 0. 001). We found no correlations between the PPARGC1A methylation level and clinical features, while the CpG₁3. 14 site methylation level was positively correlated with H-Y stage (R = 0. 246, P = 0. 020) and was increased in people carrying the rs2970848 AA genotype compared with carriers of the AG/GG genotype (7. 27 ± 1. 86 vs. 6. 65 ± 1. 92, P = 0. 032). Our results support a link between PPARGC1A methylation, gene expression and variability, which indicated a novel epigenetic regulatory mechanism controlling PPARGC1A expression influences PD pathogenesis.