Reference Intervals of Mitochondrial DNA Copy Number in Peripheral Blood for Chinese Minors and Adults

摘要

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 ofmtDNA 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 ofPOLG,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.