RGD Reference Report - Association of PGC-1alpha polymorphisms with age of onset and risk of Parkinson's disease. - Rat Genome Database

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

Authors: Clark, J  Reddy, S  Zheng, K  Betensky, RA  Simon, DK 
Citation: Clark J, etal., BMC Med Genet. 2011 May 19;12:69.
RGD ID: 6484270
Pubmed: PMID:21595954   (View Abstract at PubMed)
PMCID: PMC3112073   (View Article at PubMed Central)
DOI: DOI:10.1186/1471-2350-12-69   (Journal Full-text)

BACKGROUND: Peroxisome proliferator-activated receptor-gamma co-activator (PGC)-1alpha is a transcriptional co-activator of antioxidant genes and a master regulator of mitochondrial biogenesis. Parkinson's disease (PD) is associated with oxidative stress and mitochondrial dysfunction and recent work suggests a role for PGC-1alpha. We hypothesized that the rs8192678 PGC-1alpha single nucleotide polymorphism (SNP) may influence risk or age of onset of PD. The A10398G mitochondrial SNP has been inversely associated with risk of PD in some studies. In the current study we analyzed whether rs8192678 or other PGC-1alpha SNPs affect PD risk or age of onset, singularly or in association with the A10398G SNP. METHODS: 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. RESULTS: The rs8192678 PGC-1alpha SNP was not associated with the risk of PD. However, an association of the PGC-1alpha 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). CONCLUSIONS: These data reveal possible associations of the PGC-1alpha SNPs rs6821591 and rs2970848 with risk or age of onset of PD, and of the PGC-1alpha 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-1alpha in PD and longevity.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
PPARGC1AHumanParkinson's disease onsetIAGP DNA:SNPs:intron more ...RGD 
Ppargc1aRatParkinson's disease onsetISOPPARGC1A (Homo sapiens)DNA:SNPs:intron more ...RGD 
Ppargc1aMouseParkinson's disease onsetISOPPARGC1A (Homo sapiens)DNA:SNPs:intron more ...RGD 

Phenotype Annotations    Click to see Annotation Detail View

Manual Human Phenotype Annotations - RGD

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
PPARGC1AHumanParkinsonism onsetIAGP DNA:SNPs:intron more ...RGD 
Objects Annotated

Genes (Rattus norvegicus)
Ppargc1a  (PPARG coactivator 1 alpha)

Genes (Mus musculus)
Ppargc1a  (peroxisome proliferative activated receptor, gamma, coactivator 1 alpha)

Genes (Homo sapiens)
PPARGC1A  (PPARG coactivator 1 alpha)


Additional Information