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.