A composite peripheral blood gene expression measure as a potential diagnostic biomarker in bipolar disorder.
A composite peripheral blood gene expression measure as a potential diagnostic biomarker in bipolar disorder.
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一种复合外周血基因表达度量是双相情感障碍中潜在的诊断生物标志物。
DOI：
10.1038/tp.2015.110
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发表时间：
2015-08-04
影响因子：
6.8
通讯作者：
Kessing LV
中科院分区：
文献类型：
--
作者：
Munkholm K;Peijs L;Vinberg M;Kessing LV
外周血中的基因表达具有潜在的病理生理机制，已成为鉴定生物标记物的一条可行途径。在这里，我们的目标是识别基因表达候选基因，并探索复合基因表达测量作为双相情感障碍诊断和状态生物标记物的可能性。首先，对37例处于不同情感状态(抑郁、躁狂和欣快期)的快速循环型双相情感障碍患者和40名年龄和性别匹配的健康受试者的外周血单核细胞中19个候选基因的信使RNA水平进行了6-12个月的评估。其次，在前半个研究样本中构建了一个复合基因表达测量，并在样本的后半个样本中独立验证。我们发现，与健康对照组相比，双相情感障碍患者的Polg和OGG1表达下调。在双相情感障碍患者中，NDUFV2的上调在抑郁状态下观察到，而在愉悦状态下则是如此。基于19个基因的用于区分患者和健康对照受试者的复合基因表达测量在样本1中产生了0.81(P<；0.0001)的受试者-操作特征曲线下的面积，在样本2中重复了0.73值(P<；0.0001)，与中等精度的测试相对应。目前POLG、OGG1和NDUFV2表达变化的研究结果表明，双相情感障碍的线粒体功能和DNA修复机制存在障碍。此外，复合基因表达测量有望成为潜在的诊断生物标记物。
Gene expression in peripheral blood has the potential to inform on pathophysiological mechanisms and has emerged as a viable avenue for the identification of biomarkers. Here, we aimed to identify gene expression candidate genes and to explore the potential for a composite gene expression measure as a diagnostic and state biomarker in bipolar disorder. First, messenger RNA levels of 19 candidate genes were assessed in peripheral blood mononuclear cells of 37 rapid cycling bipolar disorder patients in different affective states (depression, mania and euthymia) during a 6–12-month period and in 40 age- and gender-matched healthy control subjects. Second, a composite gene expression measure was constructed in the first half study sample and independently validated in the second half of the sample. We found downregulation of POLG and OGG1 expression in bipolar disorder patients compared with healthy control subjects. In patients with bipolar disorder, upregulation of NDUFV2 was observed in a depressed state compared with a euthymic state. The composite gene expression measure for discrimination between patients and healthy control subjects on the basis of 19 genes generated an area under the receiver-operating characteristic curve of 0.81 (P<0.0001) in sample 1, which was replicated with a value of 0.73 (P<0.0001) in sample 2, corresponding with a moderately accurate test. The present findings of altered POLG, OGG1 and NDUFV2 expression point to disturbances within mitochondrial function and DNA repair mechanisms in bipolar disorder. Further, a composite gene expression measure could hold promise as a potential diagnostic biomarker.