Division of Molecular Biology and Human Genetics, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa; South African Medical Research Council/ Stellenbosch University Genomics of Brain Disorders Research Unit, Cape Town, South Africa.
National Health Laboratory Service (NHLS), Groote Schuur Hospital, Cape Town, South Africa; Division of Chemical Pathology, University of Cape Town, Cape Town, South Africa.
Parkinsonism Relat Disord. 2022 Aug;101:1-5. doi: 10.1016/j.parkreldis.2022.06.003. Epub 2022 Jun 15.
Altered levels of mitochondrial DNA copy number (mtDNA-CN) have been proposed as a proxy for mitochondrial dysfunction. Following reports of mtDNA depletion in the blood and substantia nigra of Parkinson's disease (PD) cases, mtDNA-CN was also suggested as a possible biomarker for PD. Therefore, this study aimed to investigate whether blood mtDNA-CN levels of African ancestry PD cases would be altered compared to controls, as previously reported in individuals of Asian and European ancestry.
Droplet digital polymerase chain reaction (ddPCR) was performed to quantify blood-derived mtDNA-CN levels as a ratio of a mitochondrial gene (MT-TL1) to a nuclear gene (B2M) in 72 PD cases and 79 controls of African ancestry (i.e. individuals with African mtDNA haplogroups) from South Africa. mtDNA-CN per cell was calculated by the formula 2 × MT-TL1/B2M.
Accepting study limitations, we report significantly higher mtDNA-CN in whole blood of our PD cases compared to controls (median difference = 81 copies/cell), independent of age (95% CI [64, 98]; P < 0.001]). These findings contradict previous reports of mtDNA depletion in PD cases.
We caution that the observed differences in mtDNA-CN between the present and past studies may be a result of unaccounted-for factors and variability in study designs. Consequently, larger well-designed investigations may help determine whether mtDNA-CN is consistently altered in the blood of PD cases across different ancestries and whether it can serve as a viable biomarker for PD.
线粒体 DNA 拷贝数（mtDNA-CN）水平的改变被认为是线粒体功能障碍的替代指标。在帕金森病（PD）病例的血液和黑质中发现 mtDNA 耗竭后，mtDNA-CN 也被认为是 PD 的潜在生物标志物。因此，本研究旨在调查非洲裔 PD 病例的血液 mtDNA-CN 水平是否与先前报道的亚洲和欧洲裔个体的水平不同。
采用数字聚合酶链反应（ddPCR）检测 72 例来自南非的非洲裔 PD 病例（即具有非洲 mtDNA 单倍群的个体）和 79 例对照者的血液衍生 mtDNA-CN 水平，以线粒体基因（MT-TL1）与核基因（B2M）的比值表示。通过公式 2×MT-TL1/B2M 计算每个细胞的 mtDNA-CN。
在考虑到研究局限性的情况下，我们报告称，与对照组相比，我们的 PD 病例的全血 mtDNA-CN 显著升高（中位数差异=81 个拷贝/细胞），与年龄无关（95%CI[64,98]；P<0.001）。这些发现与 PD 病例中 mtDNA 耗竭的先前报道相矛盾。
我们警告说，目前和过去研究中 mtDNA-CN 之间的差异可能是由于未考虑到的因素和研究设计的变异性所致。因此，更大规模的精心设计的研究可能有助于确定 mtDNA-CN 是否在不同血统的 PD 病例的血液中始终发生改变，以及它是否可以作为 PD 的可行生物标志物。
