8OHdG is not a biomarker for Huntington disease state or progression

被引:21
作者
Borowsky, Beth [1 ]
Warner, John [1 ]
Leavitt, Blair R. [2 ]
Tabrizi, Sarah J. [3 ]
Roos, Raymund A. C. [4 ]
Durr, Alexandra [5 ]
Becker, Chris [6 ]
Sampaio, Cristina [1 ]
Tobin, Allan J. [7 ]
Schulman, Howard [6 ]
机构
[1] CHDI Fdn, CHDI Management, Princeton, NJ USA
[2] Univ British Columbia, Dept Med Genet, Ctr Mol Med & Therapeut, Vancouver, BC, Canada
[3] UCL, Inst Neurol, London, England
[4] Leiden Univ, Med Ctr, Dept Neurol, Leiden, Netherlands
[5] Univ Paris 06, Hop Salpetriere, UMR S975, Dept Genet & Cytogenet, Paris, France
[6] Caprion Prote, Menlo Pk, CA USA
[7] CHDI Fdn, CHDI Management, Los Angeles, CA USA
关键词
INCREASED OXIDATIVE DAMAGE; LIQUID-CHROMATOGRAPHY; DNA; DYSFUNCTION; MARKER; MODEL;
D O I
10.1212/WNL.0b013e318293e1a1
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Objective: To evaluate plasma 8-hydroxy-deoxy-guanosine (8OHdG) levels as a potential biomarker of premanifest and early Huntington disease (HD). Methods: Personnel from 2 independent laboratories quantified 8OHdG in blinded longitudinal plasma samples taken 24 months apart from 160 TRACK-HD participants, as well as samples containing control plasma with added ("spiked") 8OHdG. One laboratory used a liquid chromatography-electrochemical array (LCECA) assay, and the other used liquid chromatography-mass spectrometry (LCMS). Results: The LCMS assay was more accurate than the LCECA assay for measurements of "spiked" 8OHdG levels in plasma. Neither assay demonstrated cross-sectional differences in plasma 8OHdG among controls, premanifest HD, and early symptomatic HD. Similarly, neither assay showed longitudinal changes in any disease group over 24 months. Conclusions: Plasma concentration of 8OHdG is not a biomarker of disease state or progression in HD. We recommend that future putative biomarker studies use blinded sample analysis, standard curves, independent analytical methods, and strict quality control of sample collection and storage. Neurology (R) 2013;80:1934-1941
引用
收藏
页码:1934 / 1941
页数:8
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