Next Generation Sequencing-Based Mitochondrial Genome Analysis In Relation To The Drug- Induced Toxicity In Korean Subjects

Background: Mitochondrial variants have been investigated to be associated with many diseases, which was reported largely from European populations. Few studies, however, have annotated the whole mitochondrial DNA (mtDNA) genome associated with drug responses including adverse drug reactions (ADRs), especially in Asian populations. This study was performed to characterize mtDNA genetic profiles, especially the distribution and frequency of well-known genetic biomarkers associated with diseases and drug-induced toxicity, in the Korean population by using high throughput next-generation sequencing.Results: A total of 681 variants was identified among all 118 Korean subjects. The MT-TRNP and displacement loop (D-loop) showed the highest numbers of variants (113 and 74 variants, respectively). In the D-loop, 25.4% of the subjects were identified to have m.16189T>C allele, which was known to reduce the mtDNA copy number variation in human cells. The variant m.1095T>C, annotated to aminoglycoside-induced ototoxicity, was found from only one subject in this study, while the frequency of m.2706A>G and m.3010A>G, which are associated with antibiotic-induced toxicity, were 99.15% and 30.51%, respectively. The 5 subjects were identified to have the variant m.2150T>TA, a genotype associated with highly disruptive effects on mitochondrial ribosomes. In addition, the mitochondrial haplogroups of 118 Korean subjects were found that D and M groups were the most dominant groups with the frequency of 34.74% and 16.1%, respectively. Conclusions: Our finding was constant with Korean 1K project and well reflected the unique profile of mitochondrial haplogroup distribution. It was the first study to annotate the whole mitochondrial genome with drug-induced toxicity to predict the ADRs event in clinical implementation for Korean population. This approach could be extended for further study for validation the potential ethnic specific mitochondrial genetic biomarkers in Korea population.