Evidence for polymerase gamma, POLG1 variation in reduced mitochondrial DNA copy number in Parkinson's disease

Background: It remains unclear whether the mtDNA content is related to the clinicopathological prognosis in Parkinson's disease (PD). Methods/Results: We analyzed the copy number of mtDNA using quantitative real-time PCR in 414 cases with PD and 231 healthy subjects from mainland of China. The level of mtDNA was significantly decreased in PD patients' peripheral blood as compared to that of healthy controls (p < 0.001). Furthermore, lower mtDNA copy number was more frequently detected (75%) in the older onset age group (>= 50 years old) than that in (49%) the younger group (<50 years old, p = 0.007), suggesting mtDNA content might be an important genetic event in PD progression. Using direct sequencing, we examined the mutations in the D-loop region of mtDNA in 318 PD patients. The results revealed that 17% of the PD patients carried mutations in the D-loop of mtDNA, and 55% of these mutations were heteroplasmic. In addition, PD patients harboring AA + AA genotype of c.2070-12T> A and c.2070-64G > A in POLG1 along with mutations in POLGI had a significantly lower copy number of mtDNA than those of PD patients without POLG1 alterations. Conclusions: Our results provided evidence for a significantly lower of mtDNA copy number in PD patients and POLG1 variation for reducing mtDNA copy number in PD. (C) 2015 Elsevier Ltd. All rights reserved.