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J Med Genet 41:e7 doi:10.1136/jmg.2003.010983
  • Electronic letters

No evidence of an association between the T16189C mtDNA variant and late onset dementia

  1. A M Gibson1,
  2. J A Edwardson1,
  3. D M Turnbull1,2,
  4. I G McKeith1,
  5. C M Morris1,
  6. P F Chinnery1,2
  1. 1Institute for Ageing and Health, Newcastle General Hospital, Newcastle upon Tyne, UK
  2. 2Department of Neurology, The University of Newcastle upon Tyne, UK
  1. Correspondence to:
 Dr P F Chinnery
 Department of Neurology, The Medical School, Framlington Place, Newcastle Upon Tyne, NE2 4HH, UK; P.F.Chinneryncl.ac.uk
  • Received 3 June 2003
  • Accepted 9 July 2003

Genetic factors are important in the aetiology of the two most common neurodegenerative diseases: Alzheimer’s disease (AD) and dementia with Lewy bodies (DLB).1,2 Individuals with AD are more likely to have a similarly affected mother than a similarly affected father,3 raising the possibility of a maternally transmitted susceptibility factor. Patients with AD accumulate cytochrome c oxidase deficient neurones at a faster rate than age matched controls,4 and although contentious, abnormal mitochondrial function has been documented in the brains of patients with AD. Cybrid studies suggest that the biochemical abnormality is due to a defect of the mitochondrial genome (mtDNA).5 Different mtDNA sequence variants have been associated with AD and DLB, but there have been no consistent findings, and a maternally transmitted susceptibility factor remains elusive.

The 16.5 kb mtDNA molecule codes for 13 essential respiratory chain subunits and the 24 RNAs required for intramitochondrial protein synthesis. Transcription and translation of mtDNA is controlled by the short 1 kb non-coding D-loop. In the wild-type genome, a thymidine residue at nucleotide position (np) 16189 interrupts a tract of cytosine residues between np 16184 and 16193, close to the origin of heavy strand replication (OH).6 The presence of a cytosine residue at np 16189 generates a homopolymeric C tract which appears to be unstable. It is thought …