Blood gene expression profiling of neurologic diseases - A pilot microarray study
Blood gene expression profiling of neurologic diseases - A pilot microarray study
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DOI：
10.1001/archneur.62.2.210
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发表时间：
2005-02-01
影响因子：
--
通讯作者：
Sharp, FR
中科院分区：
文献类型：
--
作者：
Tang, Y;Gilbert, DL;Sharp, FR
背景：组织基因表达谱与阵列测量数以千计的基因转录。然而，这种方法不能轻易地用于指导临床神经学实践。目的：确定临床神经系统疾病是否与全血中上调和下调基因的独特模式相关，并探讨外周血作为这些疾病的替代组织的可能性。设计：病例对照研究。环境：以大学为基础的儿科和成人神经病学诊所。参与者：采用传统临床标准诊断为1型神经纤维瘤病、癫痫或图雷特综合征的患者；无疾病控制；和神经系统疾病的对照组。主要观察指标：血液中12000个以上基因的表达水平，采用U95A阵列检测。结果：卡马西平或丙戊酸治疗1型神经纤维瘤病和儿童癫痫与不同的血液基因表达模式相关。丙戊酸反应性与丙戊酸难治性癫痫患者形成不同的亚群。抽动秽语综合征以几个基因表达簇为特征。在1个簇中，6个与免疫细胞功能相关的基因过表达。结论：血液基因表达谱分析可为无明显血液表型的神经系统疾病提供替代标志物。
Background: Tissue gene expression profiling with arrays measures the transcription of thousands of genes. However, this approach cannot be readily used to guide clinical neurologic practice.Objectives: To determine whether clinical neurologic diseases are associated with unique patterns of up- and down-regulated genes in whole blood and to explore the possibility of using peripheral blood as a surrogate tissue in these diseases.Design: Case-control study.Setting: University-based pediatric and adult neurology clinics.Participants: Patients with neurofibromatosis type 1, epilepsy, or Tourette syndrome diagnosed using traditional clinical criteria; controls without disease; and controls with neurologic disease.Main Outcome Measure: Blood gene expression levels of greater than 12000 genes, measured using U95A arrays.Results: Neurofibromatosis type 1 and childhood epilepsy treated with carbamazepine or valproic acid are associated with distinct patterns of blood gene expression. Patients with valproic acid-responsive vs valproic acid-refractory epilepsy formed distinct subclusters. Tourette syndrome was characterized by several gene expression clusters. In 1 cluster, 6 genes-all associated with immune cell function-were overexpressed.Conclusion: Blood gene expression profiling can provide surrogate markers for neurologic diseases without obvious blood phenotypes.