Rare POLG1 CAG variants do not influence Parkinson's disease or polymerase gamma function

Steven R Bentley; Jianguo Shan; Michael Todorovic; Stephen A Wood; George D Mellick

doi:10.1016/j.mito.2014.01.004

Rare POLG1 CAG variants do not influence Parkinson's disease or polymerase gamma function

Mitochondrion. 2014 Mar:15:65-8. doi: 10.1016/j.mito.2014.01.004. Epub 2014 Jan 31.

Authors

Steven R Bentley¹, Jianguo Shan¹, Michael Todorovic¹, Stephen A Wood¹, George D Mellick²

Affiliations

¹ Eskitis Institute for Drug Discovery, Griffith University, Brisbane, Queensland, Australia.
² Eskitis Institute for Drug Discovery, Griffith University, Brisbane, Queensland, Australia. Electronic address: g.mellick@griffith.edu.au.

PMID: 24491464
DOI: 10.1016/j.mito.2014.01.004

Abstract

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.

Keywords: CAG; Mitochondria; Neurodegeneration; POLG1; Parkinson; Trinucleotide.

MeSH terms

Australia
Case-Control Studies
DNA Polymerase gamma
DNA-Directed DNA Polymerase / genetics*
DNA-Directed DNA Polymerase / metabolism*
Disease Susceptibility
Humans
Mutant Proteins / genetics*
Mutant Proteins / metabolism*
Parkinson Disease / pathology*

Substances

Mutant Proteins
DNA Polymerase gamma
DNA-Directed DNA Polymerase
POLG protein, human