Number of CAG repeats in POLG1 and its association with Parkinson disease in the Norwegian population

The number of CAG repeats in the mitochondrial DNA-polymerase gamma (POLG1) gene has been associated with Parkinson disease (PD) in some populations. We sequenced the CAG tract of POLG1 in 191 Norwegian patients with PD and an equal number of controls and found an association between non-10 or 11 CAG repeats and PD in our population. While our results were significant, this trend was not maintained following correction for multiple testing. We also performed a meta-analysis of all published studies including our own that shows PD is associated with the number of CAG repeats in POLG1. The meta-analysis reveals that the rare allelic variation encompassed by non-10 CAG repeats associates significantly with PD (p = 0.0017). Whether this reflects a direct influence of POLG on the pathogenesis of PD or linkage disequilibrium between POLG1 alleles and nearby, disease-influencing genetic variants remains unknown.

► We studied the role of the CAG tract of POLG1 in Parkinson disease in Norway
► The number of CAG repeats in POLG1 was associated with Parkinson disease
► The strongest association was found with twelve CAG repeats
► POLG1 allelic variation may be involved in the pathogenesis of Parkinson disease
► Alternatively POLG1 variants may mark unknown nearby genetic risk factors.