8OHdG as a marker for Huntington disease progression

The PREDICT-HD Investigators and Coordinators of the Huntington Study Group

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

Leukocyte 8-hydroxydeoxyguanosine (8OHdG) is an indicator of oxidative stress, impaired metabolism, and mitochondrial dysfunction, features that have been implicated in Huntington disease (HD). Increased levels of 8OHdG have been reported in the caudate, parietal cortex, and peripherally in the serum and leukocytes, in patients diagnosed with HD. However, little is known about levels in prodromal patients and changes that might occur as the disease progresses. To address these issues, 8OHdG was tracked over time for a subset of participants enrolled in the PREDICT-HD study. Participants were stratified into four groups based on proximity to HD diagnosis at study entry: Controls (gene-negative individuals), Low (low probability of near-future diagnosis), Medium, and High. Blood samples were analyzed using Liquid Chromatography Electrochemical Array, and for comparison purposes, a separate cross-sectional sample was analyzed using liquid chromatography coupled with multiple-reaction-monitoring mass spectrometry. Longitudinal data analysis showed that initial status (at study entry) and annual rate of change varied as a function of proximity group, adjusting for sex, education, age at study entry, and site effects. Overall levels were lowest for the Control group and highest for the High group, and the rate of increase varied in a similar manner. The finding that 8OHdG concentrations increased as a function of proximity to projected disease diagnosis and duration indicates support for the continued assessment of 8OHdG as a robust clinical HD biomarker.

Original languageEnglish (US)
Pages (from-to)625-634
Number of pages10
JournalNeurobiology of Disease
Volume46
Issue number3
DOIs
StatePublished - Jun 1 2012

Fingerprint

Huntington Disease
Disease Progression
Liquid Chromatography
Leukocytes
Parietal Lobe
Sex Education
Mass Spectrometry
Oxidative Stress
Biomarkers
Control Groups
Serum
Genes

Keywords

  • 8OHdG
  • Biomarker
  • Huntington disease
  • Mitochondrial dysfunction
  • Oxidative stress
  • PREDICT-HD

ASJC Scopus subject areas

  • Neurology

Cite this

The PREDICT-HD Investigators and Coordinators of the Huntington Study Group (2012). 8OHdG as a marker for Huntington disease progression. Neurobiology of Disease, 46(3), 625-634. https://doi.org/10.1016/j.nbd.2012.02.012

8OHdG as a marker for Huntington disease progression. / The PREDICT-HD Investigators and Coordinators of the Huntington Study Group.

In: Neurobiology of Disease, Vol. 46, No. 3, 01.06.2012, p. 625-634.

Research output: Contribution to journalArticle

The PREDICT-HD Investigators and Coordinators of the Huntington Study Group 2012, '8OHdG as a marker for Huntington disease progression', Neurobiology of Disease, vol. 46, no. 3, pp. 625-634. https://doi.org/10.1016/j.nbd.2012.02.012
The PREDICT-HD Investigators and Coordinators of the Huntington Study Group. 8OHdG as a marker for Huntington disease progression. Neurobiology of Disease. 2012 Jun 1;46(3):625-634. https://doi.org/10.1016/j.nbd.2012.02.012
The PREDICT-HD Investigators and Coordinators of the Huntington Study Group. / 8OHdG as a marker for Huntington disease progression. In: Neurobiology of Disease. 2012 ; Vol. 46, No. 3. pp. 625-634.
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abstract = "Leukocyte 8-hydroxydeoxyguanosine (8OHdG) is an indicator of oxidative stress, impaired metabolism, and mitochondrial dysfunction, features that have been implicated in Huntington disease (HD). Increased levels of 8OHdG have been reported in the caudate, parietal cortex, and peripherally in the serum and leukocytes, in patients diagnosed with HD. However, little is known about levels in prodromal patients and changes that might occur as the disease progresses. To address these issues, 8OHdG was tracked over time for a subset of participants enrolled in the PREDICT-HD study. Participants were stratified into four groups based on proximity to HD diagnosis at study entry: Controls (gene-negative individuals), Low (low probability of near-future diagnosis), Medium, and High. Blood samples were analyzed using Liquid Chromatography Electrochemical Array, and for comparison purposes, a separate cross-sectional sample was analyzed using liquid chromatography coupled with multiple-reaction-monitoring mass spectrometry. Longitudinal data analysis showed that initial status (at study entry) and annual rate of change varied as a function of proximity group, adjusting for sex, education, age at study entry, and site effects. Overall levels were lowest for the Control group and highest for the High group, and the rate of increase varied in a similar manner. The finding that 8OHdG concentrations increased as a function of proximity to projected disease diagnosis and duration indicates support for the continued assessment of 8OHdG as a robust clinical HD biomarker.",
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