Heteroplasmy-associated mitochondrial dna variants in human blood and skeletal muscle samples

Objective: Mitochondrial heteroplasmy, a recognized trait in eukaryotic cells, plays a pivotal role in complex disorders like mito-chondrial diseases. High-throughput sequencing has improved precision in detecting low-level heteroplasmy and can identify ultra-low-level variants (<1%) associated with heteroplasmy attributes. We aimed to investigate potential genetic and demographic factors associated with heteroplasmy levels in mito-chondrial variants by analyzing both blood and muscle tissues in individuals, regardless of their phenotypes.Material and Methods: High-throughput sequencing was con-ducted on the mitochondrial genomes of 10 individuals, with an equal gender distribution. Variants with heteroplasmy ratios both ranging from 5% to 95% and out of this range were used for statistical analysis.Result: A total of 194 heteroplasmic variants were identified, of which 13 displayed lower heteroplasmy ratios in both blood and skeletal muscle samples from females, while the mitochondrial control region (D-Loop) exhibited higher ratios.Conclusion: The study findings confirm the correlation between the m.10398A>G variant and mitochondrial heteroplasmy levels, consistent with prior research. Additionally, we identified the m.1811A>G variant in MT-RNR2 and the m.12308A>G variant in MT-TL2, both associated with higher heteroplasmy. Conversely, the m.582T>C variant in MT-TF, m.3260A>G in MT-TL1, m.3302A>G in MT-TL1, m.4409T>C in MT-TM, and m.4267A>G in MT-TI were linked to lower heteroplasmy, all involving transition-type alterations. Furthermore, our study hinted at a potential age-related threshold for variant accumulation in the control region. Future studies, involving larger cohorts and advanced expression analysis methods, will further contribute to the validation and enhancement of these findings.