CHDI Management/CHDI Foundation, Princeton, NJ, USA.
Neurology. 2013 May 21;80(21):1934-41. doi: 10.1212/WNL.0b013e318293e1a1. Epub 2013 Apr 24.
To evaluate plasma 8-hydroxy-deoxy-guanosine (8OHdG) levels as a potential biomarker of premanifest and early Huntington disease (HD).
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).
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.
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.
评估血浆 8-羟基脱氧鸟苷（8OHdG）水平作为预测和早期亨廷顿病（HD）的潜在生物标志物。
来自 2 个独立实验室的人员对 160 名 TRACK-HD 参与者相隔 24 个月的盲法纵向血浆样本以及含有添加（“加标”）8OHdG 的对照血浆样本进行了 8OHdG 的定量检测。一个实验室使用液相色谱-电化学阵列（LCECA）检测，另一个实验室使用液相色谱-质谱法（LCMS）。
LCMS 检测法比 LCECA 检测法更能准确测量血浆中“加标”8OHdG 的水平。两种检测法都没有显示出在对照、前驱性 HD 和早期有症状的 HD 患者之间的血浆 8OHdG 存在横断面差异。同样，在 24 个月的时间内，两种检测法都没有显示出任何疾病组的纵向变化。
血浆 8OHdG 浓度不是 HD 疾病状态或进展的生物标志物。我们建议未来的潜在生物标志物研究使用盲法样本分析、标准曲线、独立分析方法以及严格的样本采集和储存质量控制。
