PMID- 34557026
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220426
IS  - 1178-7074 (Print)
IS  - 1178-7074 (Electronic)
IS  - 1178-7074 (Linking)
VI  - 14
DP  - 2021
TI  - Mutational Analysis of Mitochondrial tRNA Genes in 200 Patients with Type 2 
      Diabetes Mellitus.
PG  - 5719-5735
LID - 10.2147/IJGM.S330973 [doi]
AB  - OBJECTIVE: 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 tRNA(Leu(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.
CI  - (c) 2021 Lin et al.
FAU - Lin, Liangyan
AU  - Lin L
AD  - Department of Endocrinology and Metabolism, Yantai Affiliated Hospital of Binzhou 
      Medical University, Yantai, Shandong, People's Republic of China.
FAU - Zhang, Dongdong
AU  - Zhang D
AD  - Department of Endocrinology and Metabolism, Yantai Affiliated Hospital of Binzhou 
      Medical University, Yantai, Shandong, People's Republic of China.
FAU - Jin, Qingsong
AU  - Jin Q
AD  - Department of Endocrinology and Metabolism, Yantai Affiliated Hospital of Binzhou 
      Medical University, Yantai, Shandong, People's Republic of China.
FAU - Teng, Yaqin
AU  - Teng Y
AD  - Department of Endocrinology and Metabolism, Yantai Affiliated Hospital of Binzhou 
      Medical University, Yantai, Shandong, People's Republic of China.
FAU - Yao, Xiaoyan
AU  - Yao X
AD  - Department of Endocrinology and Metabolism, Yantai Affiliated Hospital of Binzhou 
      Medical University, Yantai, Shandong, People's Republic of China.
FAU - Zhao, Tiantian
AU  - Zhao T
AD  - Department of Endocrinology and Metabolism, Yantai Affiliated Hospital of Binzhou 
      Medical University, Yantai, Shandong, People's Republic of China.
FAU - Xu, Xinmiao
AU  - Xu X
AD  - Department of Endocrinology, Yantai Yeda Hospital, Yantai, Shandong, People's 
      Republic of China.
FAU - Jin, Yongjun
AU  - Jin Y
AD  - Department of Endocrinology and Metabolism, Yantai Affiliated Hospital of Binzhou 
      Medical University, Yantai, Shandong, People's Republic of China.
LA  - eng
PT  - Journal Article
DEP - 20210916
PL  - New Zealand
TA  - Int J Gen Med
JT  - International journal of general medicine
JID - 101515487
PMC - PMC8454214
OTO - NOTNLM
OT  - Chinese population
OT  - mitochondrial tRNA
OT  - type 2 diabetes mellitus
OT  - variants
COIS- The authors declare that they have no conflicts of interest for this work.
EDAT- 2021/09/25 06:00
MHDA- 2021/09/25 06:01
PMCR- 2021/09/16
CRDT- 2021/09/24 07:04
PHST- 2021/07/28 00:00 [received]
PHST- 2021/08/25 00:00 [accepted]
PHST- 2021/09/24 07:04 [entrez]
PHST- 2021/09/25 06:00 [pubmed]
PHST- 2021/09/25 06:01 [medline]
PHST- 2021/09/16 00:00 [pmc-release]
AID - 330973 [pii]
AID - 10.2147/IJGM.S330973 [doi]
PST - epublish
SO  - Int J Gen Med. 2021 Sep 16;14:5719-5735. doi: 10.2147/IJGM.S330973. eCollection 
      2021.