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Increased blood-derived mitochondrial DNA copy number in African ancestry individuals with Parkinson's disease
Amica Corda Müller-Nedebock1, Surita Meldau2, Carl Lombard3
1Division 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.
Introduction:
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.
Methods:
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.
Results:
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.
Conclusions:
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.
Insights
This study found higher mitochondrial DNA copy number (mtDNA-CN) in the blood of Parkinson's disease (PD) patients of African ancestry, contradicting previous findings of depletion. Further research is needed to confirm mtDNA-CN as a PD biomarker across diverse populations.
Area of Science:
- Neuroscience
- Genetics
- Biochemistry
Background:
- Mitochondrial dysfunction is implicated in Parkinson's disease (PD).
- Altered mitochondrial DNA copy number (mtDNA-CN) is a potential indicator of mitochondrial dysfunction.
- Previous studies suggested mtDNA-CN depletion in PD, but findings varied across ancestries.
Purpose of the Study:
- To investigate blood mtDNA-CN levels in Parkinson's disease (PD) cases of African ancestry.
- To determine if blood mtDNA-CN can serve as a biomarker for PD in this population.
Main Methods:
- Quantified blood mtDNA-CN using droplet digital PCR (ddPCR).
- Measured the ratio of mitochondrial gene (MT-TL1) to nuclear gene (B2M).
- Analyzed 72 PD cases and 79 controls of African ancestry from South Africa.
Main Results:
- Significantly higher mtDNA-CN observed in PD cases compared to controls (median difference = 81 copies/cell).
- This elevation was independent of age.
- Findings contradict prior reports of mtDNA depletion in PD.
Conclusions:
- Blood mtDNA-CN levels are elevated in African ancestry PD cases.
- This contradicts previous findings of mtDNA depletion in PD.
- Larger studies are needed to validate mtDNA-CN as a PD biomarker across diverse ancestries.
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