Association of PGC-1alpha polymorphisms with age of onset and risk of Parkinson's disease

Genomic DNA samples from 378 PD patients and 173 age-matched controls were analyzed by multiplexed probe sequencing, followed by statistical analyses of the association of each SNP, alone or in combination, with risk or age of onset of PD. Adjustments were made for age of onset being less than the age of sampling, and for the observed dependence between these two ages. The PD samples were obtained as two separate cohorts, therefore statistical methods accounted for different sampling methods between the two cohorts, and data were analyzed using Cox regression adjusted for sampling in the risk set definition and in the model.The rs8192678 PGC-1α SNP was not associated with the risk of PD. However, an association of the PGC-1α rs8192678 GG variant with longevity was seen in control subjects (p = 0.019). Exploratory studies indicated that the CC variant of rs6821591 was associated with risk of early onset PD (p = 0.029), with PD age of onset (p = 0.047), and with longevity (p = 0.022). The rs2970848 GG allele was associated with risk of late onset PD (p = 0.027).These data reveal possible associations of the PGC-1α SNPs rs6821591 and rs2970848 with risk or age of onset of PD, and of the PGC-1α rs8192678 GG and the rs6821591 CC variants with longevity. If replicated in other datasets, these findings may have important implications regarding the role of PGC-1α in PD and longevity.Parkinson's disease is the second most common age-related neurodegenerative disease [1]. PD is characterized in part by a loss of dopaminergic neurons in the substantia nigra, which leads to less dopamine release in the striatum and ultimately to impaired physical movement. PD is a complex disorder involving multiple genetic and environmental factors [2]. Mutations in a number of genes including α-synuclein (SNCA), Parkin, Leucine-Rich-Repeat-Kinase 2 (LRRK2), Phosphatase and Tensin (PTEN) Homolog-Induced Putative Kinase 1 (PINK1) and DJ-1 among others can cause PD or increase the risk of PD [3-