摘要 : Introduction Mutations/variants in mitochondrial genomes are found to be associated with type 2 diabetes mellitus (T2DM), but the pathophysiology of this disease remains largely unknown. Aim The aim of this study is to investigate... 展开 Introduction Mutations/variants in mitochondrial genomes are found to be associated with type 2 diabetes mellitus (T2DM), but the pathophysiology of this disease remains largely unknown. Aim The aim of this study is to investigate the relationship between mitochondrial DNA (mtDNA) variants and T2DM. Methodology A maternally inherited T2DM pedigree is underwent clinical, genetic, and molecular assessment. Moreover, the complete mitochondrial genomes of the matrilineal relatives of this family are PCR amplified and sequenced. We also utilize the phylogenetic conservation analysis, haplogroup classification, and the pathogenicity scoring system to determine the T2DM-associated potential pathogenic mtDNA variants. Result Four of seven matrilineal relatives of this pedigree suffered from T2DM with variable ages of onset. Screening for the entire mtDNA genes of matrilineal members reveals co-existence of ND5 T12338C and tRNA(Ala) T5587C variants, as well as 21 genetic polymorphisms which belong to East Asian haplogroup F2. Interestingly, the T12338C variant causes the alternation of first amino acid Met to Thr, shortened two amino acids of ND5 protein. Furthermore, T5587C variant is located at position 73 in the 3'end of mt-tRNA(Ala) and may have structural and functional consequences. Conclusions The co-occurrence of ND5 T12338C and tRNA(Ala) T5587C variants may impair the mitochondrial function, which are associated with the development of T2DM in this family. 收起