• X Geng, Y Zhang, J Yan, C Chu, F Gao, Z Jiang, X Zhang, Y Chen, X Wei, Y Feng, H Lu, C Wang, F Zeng, and W Jia.
• Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai Key Laboratory of Diabetes, Shanghai, China.
• Diabet. Med. 2019 Jun 1; 36 (6): 776-783.

AimsTo investigate the associations among heteroplasmy levels (i.e. the proportions of mutant and wild-type mitochondrial DNA in the same cell), mitochondrial function and clinical severity of the m.3243A>G mutation.MethodsA total of 17 participants carrying the m.3243A>G mutation and 17 sex- and age-matched healthy controls were included in this study. Heteroplasmy levels of the m.3243A>G mutation in leukocytes, saliva and urine sediment were determined by pyrosequencing. The clinical evaluation included endocrinological, audiological and ophthalmological examinations. Mitochondrial function was determined in peripheral blood mononuclear cells isolated from participants.ResultsHeteroplasmy levels in urine sediment were higher than those in leukocytes and saliva. Reduced levels of adenosine triphosphate and mitochondrial membrane potential, and increased reactive oxygen species production were observed in mutant peripheral blood mononuclear cells (all P < 0.05). Linear regression analysis indicated that higher heteroplasmy levels in peripheral blood leukocytes were associated with increased levels of glycated albumin and HbA1c , and decreased total hip bone mineral density T-score after adjustment for age and sex (all P < 0.05). Furthermore, mitochondrial membrane potential was independently associated with bone mineral density T-score at the femoral neck (P < 0.05).ConclusionsHeteroplasmy levels in peripheral blood leukocytes and mitochondrial membrane potential in peripheral blood mononuclear cells were closely associated with clinical manifestations and were valuable for evaluation of the clinical severity of the m.3243A>G mutation.© 2018 Diabetes UK.

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