Correlation between methylation and copy number of mitochondrial DNA D-loop region in peripheral blood and Parkinson's disease

  Background  Parkinson's disease (PD) is a neurodegenerative disease that occurs mostly in middle-aged and elderly people. Mitochondrial DNA (mtDNA) methylation may be involved in the pathogenesis and progression of PD, but there are few related studies.

  Objective  To observe the changes in methylation level of the D-loop region and the mtDNA copy number in peripheral blood of PD patients, analyze the correlation between them, so as to explore the potential involvement of mtDNA methylation in the pathogenesis of PD.

  Methods  Totally 30 PD patients and 30 age and sex-matched normal controls (66.63 ± 7.95 years vs 63.50 ± 4.96 years) were selected from the First Affiliated Hospital of Baotou Medical College from 2020 to 2022, including 15 males and 15 females in this case-control study. The D-loop methylation analyses in peripheral blood were performed using mass spectrometry (MassARRAY), and the mtDNA copy number was detected by quantitative real-time PCR analysis (qRT-PCR).

  Results  There was no significant difference in the overall methylation level and the methylation level of each CpG site of the D-loop region in peripheral blood between PD group and control group, and no significant difference was found between early and advanced PD patients either (P>0.05). The mtDNA copy number in peripheral blood of PD group was lower than that of controls (P=0.02), and the mtDNA copy number of advanced PD patients was lower than that of early PD patients (P=0.012). The methylation levels of CpG sites 1, 15 in the D-loop region were negatively correlated with the mtDNA copy number (r=-0.257, P=0.047; r=-0.517, P＜0.001). Binary Logistic regression analysis showed that more mtDNA copy number was associated with lower likelyhood of PD (OR=0.119, P=0.023).

  Conclusion  The methylation level of D-loop region in peripheral blood of PD patients does not change significantly, but the mtDNA copy number in peripheral blood of PD patients decreases dynamically with the progression of PD, which will be an index to predict the pathogenesis and progression of PD. The methylation of the D-loop region may negatively regulate mtDNA replication and transcription.