Ya-Xing Gui1, Zhong-Ping Xu2, Wen Lv1, Jin-Jia Zhao1, Xing-Yue Hu3. 1. Department of Neurology, Sir Run Run Shaw Hospital, Affiliated with School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310016, China. 2. Department of Medicine, The University of Chicago, Chicago, IL 60637, USA. 3. Department of Neurology, Sir Run Run Shaw Hospital, Affiliated with School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310016, China. Electronic address: Huxingyue2003@163.com.
Abstract
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 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.
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 PDpatients' 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 PDpatients. The results revealed that 17% of the PDpatients carried mutations in the D-loop of mtDNA, and 55% of these mutations were heteroplasmic. In addition, PDpatients 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 PDpatients without POLG1 alterations. CONCLUSIONS: Our results provided evidence for a significantly lower of mtDNA copy number in PDpatients and POLG1 variation for reducing mtDNA copy number in PD.
Authors: Amica C Müller-Nedebock; Rebecca R Brennan; Marianne Venter; Ilse S Pienaar; Francois H van der Westhuizen; Joanna L Elson; Owen A Ross; Soraya Bardien Journal: Neurochem Int Date: 2019-06-21 Impact factor: 3.921
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