title: Mitochondrial gene variation in type 2 diabetes mellitus: detection of a novel mutation associated with maternally inherited diabetes in a Chinese family.
abstract: OBJECTIVE
  To explore the relationship between type 2 diabetes mellitus and the mutation(s) in mitochondrial DNA.
  
  
  METHODS
  According to the previous literature, the fragment of mitochondrial DNA from nucleotide 3153 to 3551, which had shown high frequency of point mutation, was scanned with the technique of polymerase chain reaction--single strand conformation polymorphism (PCR-SSCP) in Chinese normal control, type 2 diabetic population, and 12 families suffered from maternally inherited type 2 diabetes mellitus. Direct sequencing was applied to detect the fragments with abnormal conformation.
  
  
  RESULTS
  No special band was found in SSCP electrophoreses in Chinese normal control, and only one subject (No. 81) of diabetic population indicated the abnormality in SSCP study, which was affirmed to be a silent point mutation of T to C at nucleotide 3336 inducing no change in amino acid (ATT-->ATC, Ile). Pedigree 25,001 was the only family that exhibited strongly different SSCP characteristic from the other 11 ones, which was confirmed to be caused by a single point mutation mt3285T-->C/T in the coding region of tRNA(Leu(UUR)) gene by the technique of direct sequencing.
  
  
  CONCLUSIONS
  The variation within mt DNA 3153-3551 is not the major cause of type 2 diabetes in Chinese population suffered from this disease in this study. The point mutation T-->C/T at the mitochondrial nucleotide 3285, which was found in pedigree 25,001, is located in the highly conservative region of tRNA(Leu(UUR)) gene. It is strongly suggested that this mutation cause the conversion in the 3-dimentional structure of tRNA(Leu(UUR)), which might disturb the normal translation and lead to the impairment in mitochondrial oxidative phosphorylation characterized by the defects of the polypeptides involved in the respiratory chain. Thus, insulin secretion deficiency and insulin resistance might occur.
authors.affiliation: Department of Endocrinology, First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China. ljma@jlonline.com
authors.forename: L
authors.initials: L
authors.lastname: Ma
authors.forename: H
authors.initials: H
authors.lastname: Wang
authors.forename: J
authors.initials: J
authors.lastname: Chen
authors.forename: W
authors.initials: W
authors.lastname: Jin
authors.forename: L
authors.initials: L
authors.lastname: Liu
authors.forename: B
authors.initials: B
authors.lastname: Ban
authors.forename: J
authors.initials: J
authors.lastname: Shen
authors.forename: Z
authors.initials: Z
authors.lastname: Hua
authors.forename: J
authors.initials: J
authors.lastname: Chai
mesh_terms: D000328:Adult; D000368:Aged; D019943:Amino Acid Substitution; D001483:Base Sequence; D002681:China; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004252:DNA Mutational Analysis; D004272:DNA, Mitochondrial / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000473:pathology; D005192:Family Health; D005260:Female; D014644:Genetic Variation; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D017354:Point Mutation; D018807:Polymorphism, Single-Stranded Conformational; D012356:RNA, Transfer, Leu / Q000235:genetics; D016415:Sequence Alignment; D012689:Sequence Homology, Nucleic Acid
chemical_list: D004272:DNA, Mitochondrial; D012356:RNA, Transfer, Leu; D004247:DNA