Journal article
8OHdG as a marker for Huntington disease progression
Neurobiology of disease, Vol.46(3), pp.625-634
06/2012
DOI: 10.1016/j.nbd.2012.02.012
PMCID: PMC3784019
PMID: 22414782
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.
► 8OHdG is an indicator of oxidative stress and implicated in Huntington disease. ► Little is known about levels of 8OHdG in prodromal patients. ► PREDICT-HD participants were stratified into risk groups and followed over time. ► Growth rate increased as proximity to projected disease diagnosis increased. ► Results shows evidence 8OHdG is a robust clinical Huntington disease biomarker.
Details
- Title: Subtitle
- 8OHdG as a marker for Huntington disease progression
- Creators
- Jeffrey D Long - The University of Iowa Carver College of Medicine, Department of Psychiatry, Iowa City, IA, USAWayne R Matson - Edith Nourse Rogers Memorial VA Hospital, Bedford, MA, USAAndrew R Juhl - Department of Psychological and Quantitative Foundations, University of Iowa, Iowa City, IA, USABlair R Leavitt - University of British Columbia, Department of Medical Genetics, Vancouver, BC, CanadaJane S Paulsen - The University of Iowa Carver College of Medicine, Department of Psychiatry, Iowa City, IA, USAPREDICT-HD Investigators and Coordinators of the Huntington Study Group
- Resource Type
- Journal article
- Publication Details
- Neurobiology of disease, Vol.46(3), pp.625-634
- DOI
- 10.1016/j.nbd.2012.02.012
- PMID
- 22414782
- PMCID
- PMC3784019
- NLM abbreviation
- Neurobiol Dis
- ISSN
- 0969-9961
- eISSN
- 1095-953X
- Publisher
- Elsevier Inc
- Language
- English
- Date published
- 06/2012
- Academic Unit
- Psychiatry; Psychological and Brain Sciences; Biostatistics
- Record Identifier
- 9984003482702771
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