International Journal of General Medicine (Sep 2021)

Mutational Analysis of Mitochondrial tRNA Genes in 200 Patients with Type 2 Diabetes Mellitus

  • Lin L,
  • Zhang D,
  • Jin Q,
  • Teng Y,
  • Yao X,
  • Zhao T,
  • Xu X,
  • Jin Y

Journal volume & issue
Vol. Volume 14
pp. 5719 – 5735


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Liangyan Lin,1 Dongdong Zhang,1 Qingsong Jin,1 Yaqin Teng,1 Xiaoyan Yao,1 Tiantian Zhao,1 Xinmiao Xu,2 Yongjun Jin1 1Department of Endocrinology and Metabolism, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, Shandong, People’s Republic of China; 2Department of Endocrinology, Yantai Yeda Hospital, Yantai, Shandong, People’s Republic of ChinaCorrespondence: Yongjun JinDepartment of Endocrinology and Metabolism, Yantai Affiliated Hospital of Binzhou Medical University, Jinbu Street No. 717, Yantai, 264100, People’s Republic of ChinaTel/Fax +86 535-4770613Email [email protected]: Previous studies showed that variants in mitochondrial DNA (mtDNA) are associated with type 2 diabetes mellitus (T2DM). However, the relationships between mitochondrial tRNA (mt-tRNA) variants and T2DM remain poorly understood.Methods: In this study, we performed a mutational screening of 22 mt-tRNA genes in a cohort of 200 Han Chinese subjects with T2DM and 200 control subjects through PCR–Sanger sequencing. The identified mt-tRNA variants were assessed for their pathogenicity via the phylogenetic approach, structural and functional analysis. Furthermore, two Han Chinese pedigrees with maternally inherited diabetes and deafness (MIDD) were reported by clinical and genetic assessments.Results: A total of 49 genetic variants in mt-tRNA genes were identified; among them, 31 variants (17 pathogenic/likely pathogenic) were absent in controls, located at extremely conserved nucleotides, may have potential structural and functional significance, thereby considered to be T2DM-associated variants. In addition, sequence analysis of entire mitochondrial genomes of the matrilineal relatives from two MIDD pedigrees revealed the occurrence of tRNALeu(UUR) A3243G and T3290C mutations, as well as sets of polymorphisms belonging to mitochondrial haplogroups F2 and D4. However, the lack of any functional variants in connexin 26 gene (GJB2) and tRNA 5-methylaminomethyl-2-thiouridylate (TRMU) suggested that nuclear genes may not play active roles in clinical expression of MIDD in these pedigrees.Conclusion: Our data indicated that mt-tRNA variants were associated with T2DM, screening for mt-tRNA pathogenic mutations was recommended for early detection and prevention of mitochondrial diabetes.Keywords: type 2 diabetes mellitus, mitochondrial tRNA, variants, Chinese population