title: Evidence for polymerase gamma, POLG1 variation in reduced mitochondrial DNA copy number in Parkinson's disease.
abstract: BACKGROUND
  It remains unclear whether the mtDNA content is related to the clinicopathological prognosis in Parkinson's disease (PD).
  
  
  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 POLG1 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.
authors.affiliation: Department of Neurology, Sir Run Run Shaw Hospital, Affiliated with School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310016, China.
authors.forename: Ya-Xing
authors.initials: YX
authors.lastname: Gui
authors.affiliation: Department of Medicine, The University of Chicago, Chicago, IL 60637, USA.
authors.forename: Zhong-Ping
authors.initials: ZP
authors.lastname: Xu
authors.affiliation: Department of Neurology, Sir Run Run Shaw Hospital, Affiliated with School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310016, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Lv
authors.affiliation: Department of Neurology, Sir Run Run Shaw Hospital, Affiliated with School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310016, China.
authors.forename: Jin-Jia
authors.initials: JJ
authors.lastname: Zhao
authors.affiliation: Department of Neurology, Sir Run Run Shaw Hospital, Affiliated with School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310016, China. Electronic address: Huxingyue2003@163.com.
authors.forename: Xing-Yue
authors.initials: XY
authors.lastname: Hu
mesh_terms: D000368:Aged; D056915:DNA Copy Number Variations / Q000235:genetics*; D004252:DNA Mutational Analysis; D000074002:DNA Polymerase gamma; D004259:DNA-Directed DNA Polymerase / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000235:genetics*; D013223:Statistics as Topic
chemical_list: D000074002:DNA Polymerase gamma; D004259:DNA-Directed DNA Polymerase; C413027:POLG protein, human
keywords: Mitochondrial DNA; POLG1; Parkinson's diseases