講演情報
[O31-3]慢性腎臓病におけるミトコンドリア変異について
○金指 勇樹1, 前嶋 和紘1, Todd Johnson1, 軸屋 良介2, 蓮見 壽史2, 前川 滋克3, 小原 航3, 中川 英刀1 (1.理化学研究所 生命医科学研究センター, 2.横浜市立大学 泌尿器科学教室, 3.岩手医科大学 泌尿器科学講座)
Mitochondria genome (mtDNA) is circular DNA with a length of 16.6 kb, encoding 13 proteins necessary for oxidative phosphorylation and tRNAs. Recent studies show that mitochondrial damage or dysfunction may have some roles in the pathogenesis of kidney injury, such as acute kidney injury, chronic kidney disease (CKD), and kidney cancers. However, somatic mtDNA mutations or heteroplasmy in injured kidneys are not explored yet. To analyze mtDNA variants, we performed long-range PCR and ultra-deep sequencing (30000x) from DNAs of 78 kidney tissues including grade 5 CKD. Our analytical pipeline found that deleterious mutations, such as nonsense, frameshift and pathogenic tRNA, were more frequently observed in CKD grade 5 than grade 1 in low-level heteroplasmy. Homoplasmic missense variants related to mitochondrial disease were also found in grade 5 CKD tissues. These results suggest that deleterious mutations in mtDNA may be accumulated during CKD progression, related with kidney dysfunction.