Rare POLG1 CAG variants do not influence Parkinson's disease or polymerase gamma function.
A recent meta-analysis suggested that rare CAG repeat variants in the gene that encodes polymerase gamma (POLG1) predispose individuals to develop Parkinson's disease (PD); alternative alleles were proposed to increase risk by 27%. In the current case-control study of 2255 Australians, we observed no statistical association between individuals possessing rare CAG repeat genotypes and PD (p=0.178); a subsequent meta-analysis of 2852 PD cases and 2833 controls was also non-significant (OR=1.085, p=0.124). Moreover, mitochondrial DNA synthesis (p=0.427) or Complex I activity (p=0.639) were not different in cells derived from individuals with different POLG1 genotypes. These data provide no evidence to suggest CAG repeat length in POLG1 affects PD susceptibility.
Eskitis Institute for Drug Discovery, Griffith University, Brisbane, Queensland, Australia.
Steven R
SR
Bentley
Eskitis Institute for Drug Discovery, Griffith University, Brisbane, Queensland, Australia.
Jianguo
J
Shan
Eskitis Institute for Drug Discovery, Griffith University, Brisbane, Queensland, Australia.
Michael
M
Todorovic
Eskitis Institute for Drug Discovery, Griffith University, Brisbane, Queensland, Australia.
Stephen A
SA
Wood
Eskitis Institute for Drug Discovery, Griffith University, Brisbane, Queensland, Australia. Electronic address: g.mellick@griffith.edu.au.
George D
GD
Mellick
D001315:Australia; D016022:Case-Control Studies; D000074002:DNA Polymerase gamma; D004259:DNA-Directed DNA Polymerase / Q000235:genetics* / Q000378:metabolism*; D004198:Disease Susceptibility; D006801:Humans; D050505:Mutant Proteins / Q000235:genetics* / Q000378:metabolism*; D010300:Parkinson Disease / Q000473:pathology*
D050505:Mutant Proteins; D000074002:DNA Polymerase gamma; D004259:DNA-Directed DNA Polymerase; C413027:POLG protein, human
CAG; Mitochondria; Neurodegeneration; POLG1; Parkinson; Trinucleotide