Novel mitochondrial 16S rRNA mutation, 3200T-->C, associated with adult-onset type 2 diabetes

Chin Med J (Engl). 2002 May;115(5):753-8.

Abstract

Objective: To investigate the role of a potential diabetes-related mitochondrial region, which includes two previously reported mutations, 3243A-->G and 3316G-->A, in Chinese patients with adult-onset type 2 diabetes.

Methods: A total of 277 patients and 241 normal subjects were recruited for the study. Mitochondrial nt 3116 - 3353, which spans the 16S rRNA, tRNA(leu(UUR)) and the NADH dehydrogenase 1 gene, were detected using polymerase chain reaction (PCR), direct DNA sequencing, PCR-restriction fragment length polymorphism and allele-specific PCR. Variants were analyzed by two-tailed Fisher exact test. The function of the variants in 16S rRNA were predicted for minimal free energy secondary structures by RNA folding software mfold version 3.

Results: Four homoplasmic nucleotide substitutions were observed, 3200T-->C, 3206C-->T, 3290T-->C and 3316G-->A. Only the 3200T-->C mutation is present in the diabetic population and absent in the control population. No statistically significant associations were found between the other three variants and type 2 diabetes. The 3200T-->C and 3206C-->T nucleotide substitutions located in 16S rRNA are novel variants. The 3200T-->C caused a great alteration in the minimal free energy secondary structure model while the 3206C-->T altered normal 16S rRNA structure little.

Conclusions: The results suggest that the 3200T-->C mutation is linked to the development of type 2 diabetes, but that the other observed mutations are neutral. In contrast to the Japanese studies, the 3316G-->A does not appear to be related to type 2 diabetes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age of Onset
  • Aged
  • Alleles
  • Base Sequence
  • DNA Mutational Analysis
  • DNA, Mitochondrial / chemistry
  • DNA, Mitochondrial / genetics*
  • Diabetes Mellitus, Type 2 / genetics*
  • Humans
  • Middle Aged
  • Models, Molecular
  • Nucleic Acid Conformation
  • Point Mutation
  • Polymerase Chain Reaction / methods
  • Polymorphism, Restriction Fragment Length
  • RNA, Ribosomal, 16S / chemistry
  • RNA, Ribosomal, 16S / genetics*

Substances

  • DNA, Mitochondrial
  • RNA, Ribosomal, 16S