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 regulating the PGC-1α expression is still limited. We sought to determine whether the epigenetic modification of (the gene encoding PGC-1α) could account for its diminished expression. We performed a study of risk-SNP genotypes, methylation level, and the expression in blood from 171 subjects. The mean DNA methylation level of intron 1 in patients with PD was higher than that in the controls (7.18 ± 1.74 vs. 6.36 ± 1.28, = 0.007). A detailed comparison of the DNA methylation level at each CpG site showed that CpG_1, CpG_13.14, CpG_17.18, and CpG_20 were significantly hypermethylated in patients with PD. There was a significant negative correlation between methylation and expression level ( = -0.404, < 0.001). We found no correlations between the methylation level and the clinical features, while the CpG_13.14 site methylation level was positively correlated with H&Y stage ( = 0.246, = 0.020) and was increased in people carrying the rs2970848 AA genotype compared with that in carriers of the AG/GG genotype (7.27 ± 1.86 vs. 6.65 ± 1.92, = 0.032). Our results support a link between methylation, gene expression, and variability, which indicated that a novel epigenetic regulatory mechanism controlling expression influences PD pathogenesis.