Background: Mitochondrial DNA (mtDNA) content measured by different techniques cannot be compared between studies, and age- and tissue-related control values are hardly available. In the present study, we aimed to establish the normal reference range of mtDNA copy number in the Chinese population.
Methods: Two healthy cohorts of 200 Chinese minors (0.1-18.0 years) and 200 adults (18.0-88.0 years) were recruited. Then, they were further categorized into eight age groups. The absolute mtDNA copy number per cell was measured by a quantitative real-time polymerase chain reaction. We subsequently used this range to evaluate mtDNA content in four patients (0.5-4.0 years) with molecularly proven mitochondrial depletion syndromes (MDSs) and 83 cases of mitochondrial disease patients harboring the m.3243A>G mutation.
Results: The reference range of mtDNA copy number in peripheral blood was 175-602 copies/cell (mean: 325 copies/cell) in minors and 164-500 copies/cell (mean: 287 copies/cell) in adults. There was a decreasing trend in mtDNA copy number in blood with increasing age, especially in 0-2-year-old and >50-year-old donors. The mean mtDNA copy number level among the mitochondrial disease patients with m.3243A>G mutation was significantly higher than that of healthy controls. The mtDNA content of POLG, DGUOK, TK2, and SUCLA2 genes in blood samples from MDS patients was reduced to 25%, 38%, 32%, and 24%, respectively.
Conclusions: We primarily establish the reference intervals of mtDNA copy number, which might contribute to the clinical diagnosis and monitoring of mitochondrial disease.