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Mitochondrial DNA Copy Number High in Parkinson’s Patients in S. Africa

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People of African ancestry in South Africa with Parkinson’s disease have more copies of mitochondrial DNA within their cells than do people of similar ancestry without the condition, a study discovered.

These findings contrast with studies in patients of Asian and European ancestry, who have fewer copy numbers than those without Parkinson’s.

Further work is needed to determine if the number of mitochondrial DNA (mtDNA) copies consistently differs across patients of different ancestries, and whether mtDNA can be a suitable biomarker for Parkinson’s, the researchers noted.

The study “Increased blood-derived mitochondrial DNA copy number in African ancestry individuals with Parkinson’s disease”Was published in the journal Parkinsonism and Related Disorders..

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Problems in the workings of mitochondria — structures within cells that generate energy — are thought to contribute to the loss of dopamine-producing nerve cells in the brain that causes Parkinson’s.

Separate from the primary genome in the cell, mitochondria have their own genome in the form of small, circular segments of DNA, known as mtDNA. MtDNA contains genes, inherited exclusively from the mother, that provide instructions for some mitochondrial proteins.

Because a sufficient number of mtDNA copies are essential for normal energy production, the mtDNA copy number has been proposed as a marker of mitochondrial function.

Studies suggest that mtDNA copy numbers are significantly lower in people with Parkinson’s, especially in nerve cells found in the most affected areas of the brain. However, these studies have focused on patients of European and Asian ancestry.

To investigate mtDNA copy numbers in patients of African ancestry, researchers based at Stellenbosch University, in the country’s Western Cape province, recruited 72 individuals (53% female) with late-stage Parkinson’s disease.

“This was the first study to report on mtDNA-CN [copy number] in a collection of African ancestry [Parkinson’s disease] cases, ”the team wrote.

Eligible participants self-identified as’Black’ South Africans and carried an African-specific mtDNA haplogroup, a genetic marker of related ancestry. A group of 79 ancestry-matched controls was included as a comparison.

Analysis of DNA in blood samples revealed that, overall, Parkinson’s patients had significantly higher mtDNA copy numbers compared to controls (median of 194 vs. 118).

Because controls were significantly older than patients (median age, 77 vs. 64), and mtDNA copies are known to decrease with age, the findings were adjusted for age.

Regardless, the median difference in mtDNA copy number between the two groups remained significantly different at 81 copies per cell. Consistently, even after comparing subgroups of participants without an age difference, patients had significantly more mtDNA copies than controls.

“We present intriguing findings of increased mtDNA-CN that contradict previous reports of mtDNA depletion in the blood of [Parkinson’s disease] cases, ”the researchers wrote, and thus“ consider the possibility of both significantly increased and decreased levels of mtDNA being indicators of impaired mitochondrial function. ”

The researchers caution that these varying results may reflect study design or unaccounted-for influencing factors.

Participants were also screened for mutations in the MPV17 gene, which encodes for a mitochondrial protein thought to play a role in maintaining mtDNA copy number.

Mutations in this gene, previously found at a high frequency in the African population of South Africa (1 in 68), cause mtDNA depletion syndrome, characterized by liver disease and neurological problems that begin in infancy.

Only one 57-year-old woman with Parkinson’s carried the mutation; she had no family history of Parkinson’s and disease onset at age 55. Unexpectedly, the researchers noted, she had the highest mtDNA copy number of all study participants, with 379 mtDNA copies per cell.

“It may be worthwhile investigating mtDNA-CN in a group of known MPV17 variant carriers vs controls to determine whether carriers have higher levels of mtDNA-CN, ”the team added.

This study “found significantly increased mtDNA-CN levels in the whole blood of African ancestry [Parkinson’s disease] cases compared to controls, ”the scientists concluded.

“Larger well-designed investigations may help determine whether mtDNA-CN is consistently altered in the blood of [Parkinson’s disease] cases across different ancestries and whether it can serve as a viable biomarker ”for Parkinson’s.

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