Mitochondrial genome polymorphisms associated with type-2 diabetes or obesity

Mitochondrion. 2005 Feb;5(1):15-33. doi: 10.1016/j.mito.2004.09.001.


Although a strong correlation between type-2 diabetes and obesity has been found, no comparative analysis between diabetes and obesity has been performed with respect to mitochondrial DNA (mtDNA) polymorphisms. To test the hypothesis that certain mitochondrial single nucleotide polymorphisms (mtSNPs) might be associated with obesity or type-2 diabetes, we determined the entire sequences of the mitochondrial genomes from 96 patients with type-2 diabetes and those from 96 young obese adults by direct sequencing and compared the frequencies of mtSNPs between these two groups. A mtSNP, 8684C > T (T53I) in the mitochondrial ATP synthase subunit 6 gene (ATP6), was detected in 5 of the 96 patients with type-2 diabetes, whereas this substitution was not detected in any of the 96 young obese adults. Two mtSNPs, 3497C > T (A64V) in NADH dehydrogenase subunit 1 gene (ND1) and 1119T > C (472U > C) in the 12S rRNA gene, were detected in 5 of the 96 young obese adults, whereas these substitutions were not detected in any of the 96 diabetic patients. The 8684C > T transition associated with type-2 diabetes represents haplogroup M8a, and the 3497C > T and 1119T > C transitions predisposing to obesity represent haplogroup B4c. These results suggest that distinct mtSNPs contribute to susceptibility to type-2 diabetes or obesity, pointing out the necessity of large-scale case control studies.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Amino Acid Substitution
  • Animals
  • Base Sequence
  • DNA, Mitochondrial / genetics*
  • Diabetes Mellitus, Type 2 / genetics*
  • Genome, Human
  • Humans
  • Japan
  • Mammals / genetics
  • Middle Aged
  • Mitochondrial Proteins / chemistry
  • Mitochondrial Proteins / genetics
  • Mitochondrial Proton-Translocating ATPases / chemistry
  • Mitochondrial Proton-Translocating ATPases / genetics
  • Models, Molecular
  • Molecular Sequence Data
  • NADH Dehydrogenase / genetics
  • Nucleic Acid Conformation
  • Obesity / genetics*
  • Phylogeny
  • Polymorphism, Single Nucleotide*
  • Protein Structure, Secondary
  • RNA, Ribosomal / chemistry
  • RNA, Ribosomal / genetics
  • RNA, Transfer / chemistry
  • RNA, Transfer / genetics


  • DNA, Mitochondrial
  • MT-ATP6 protein, human
  • Mitochondrial Proteins
  • RNA, Ribosomal
  • RNA, ribosomal, 12S
  • RNA, Transfer
  • NADH Dehydrogenase
  • Mitochondrial Proton-Translocating ATPases