Mitochondrial DNA levels in Huntington disease leukocytes and dermal fibroblasts

Metab Brain Dis. 2017 Aug;32(4):1237-1247. doi: 10.1007/s11011-017-0026-0. Epub 2017 May 16.

Abstract

Huntington disease (HD) is an inherited neurodegenerative disorder caused by mutations in the huntingtin gene. Involvement of mitochondrial dysfunctions in, and especially influence of the level of mitochondrial DNA (mtDNA) on, development of this disease is unclear. Here, samples of blood from 84 HD patients and 79 controls, and dermal fibroblasts from 10 HD patients and 9 controls were analysed for mtDNA levels. Although the type of mitochondrial haplogroup had no influence on the mtDNA level, and there was no correlation between mtDNA level in leukocytes in HD patients and various parameters of HD severity, some considerable differences between HD patients and controls were identified. The average mtDNA/nDNA relative copy number was significantly higher in leukocytes, but lower in fibroblasts, of symptomatic HD patients relative to the control group. Moreover, HD women displayed higher mtDNA levels in leukocytes than HD men. Because this is the largest population analysed to date, these results might contribute to explanation of discrepancies between previously published studies concerning levels of mtDNA in cells of HD patients. We suggest that the size of the investigated population and type of cells from which DNA is isolated could significantly affect results of mtDNA copy number estimation in HD. Hence, these parameters should be taken into consideration in studies on mtDNA in HD, and perhaps also in other diseases where mitochondrial dysfunction occurs.

Keywords: Dermal fibroblasts; Haplogroup; Huntington disease; Leukocytes; Mitochondrial DNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • DNA, Mitochondrial / genetics
  • DNA, Mitochondrial / metabolism*
  • Female
  • Fibroblasts / metabolism*
  • Humans
  • Huntington Disease / genetics
  • Huntington Disease / metabolism*
  • Leukocytes / metabolism*
  • Male
  • Middle Aged
  • Mutation
  • Skin / metabolism
  • Young Adult

Substances

  • DNA, Mitochondrial