Genomics of Pediatric Headache Disorders

描述(申请人提供)：这个项目将检测偏头痛患者血液中的基因表达。我们使用微阵列显示了大鼠在缺血、出血、癫痫持续状态和胰岛素诱导的低血糖后有独特的血液基因组图谱。最近在人类中的研究结果表明，性别和年龄对血液基因组的表达有深远的影响，Y染色体上的基因区分男性和女性血液样本，淋巴细胞特异性基因随着年龄的增加而减少。 我们还展示了一种常染色体显性遗传病--1型神经纤维瘤病的血液基因组图谱。我们推测偏头痛是一种非孟德尔遗传性疾病，具有特定的血液基因组图谱。事实上，我们的初步数据表明，患有急性、间歇性、偏头痛的儿童和患有慢性日常头痛的儿童都有特定的血液基因组图谱，这些图谱彼此相似，但与患有其他神经系统疾病的对照组儿童或健康对照组不同。这项建议旨在证实这些初步发现，并确定急性偏头痛和慢性日常头痛患者的血液基因组谱是否相似或不同，以及与那些需要曲坦作为抢救药物的患者相比，对非类固醇抗炎药(NSAIDs)有反应的患者的血液基因组谱是否不同。这项研究涉及在头痛期间和头痛缓解期间从偏头痛和慢性日常头痛患者身上采集血液样本(内部对照)，并将这些样本与没有偏头痛或偏头痛家族史的对照组患者进行比较。来自全血的RNA被分离、标记并应用于人类寡核苷酸微阵列，这些微阵列调查了人类的大部分基因组。最近开发的统计程序被用来识别与对照患者相比在头痛中调节的潜在转录本。在每次比较中，将使用定量、实时RT-PCR来确认这些受调控的基因。这项研究的结果应该有助于开始开发一种分子基因组方法来诊断和治疗不同的头痛疾病。

DESCRIPTION (provided by applicant): This project will examine gene expression in the blood of patients with migraine. We have used microarrays to show that there are unique blood genomic profiles in rats following ischemia, hemorrhage, status epilepticus, and insulin-induced hypoglycemia. Recent results in humans demonstrate that gender and age have profound effects on blood genomic expression, with genes on the Y-chromosome distinguishing male from female blood samples, and lymphocyte-specific genes decreasing with older age. We have also shown a specific blood genomic profile for Neurofibromatosis type 1, an autosomal dominant disease. We postulated that migraine, a non-Mendelian, hereditary disease, will have a specific blood genomic profile. Indeed, our preliminary data demonstrate that children with both acute, episodic, migraine headaches and children with chronic daily headaches have specific blood genomic profiles that are similar to each other but different from control children with other neurological diseases or to healthy controls. This proposal is designed to confirm these initial findings, and to determine whether acute migraine and chronic daily headache patients have similar or different blood genomic profiles, and whether there is a different blood genomic profile in patients that respond to NSAIDs (non-steroidal anti-inflammatory drugs) compared to those patients that require triptans as rescue medication. The study involves taking blood samples from patients with migraine and chronic daily headaches during the headaches and during headache free intervals (internal control), and comparing these to control patients without migraine or a family history of migraine. RNA from whole blood is isolated, labeled and applied to human oligonucleotide microarrays that survey most of the human genome. Recently developed statistical programs are used to identify potential transcripts regulated in headache compared to control patients. Quantitative, real time RT-PCR will be used to confirm these regulated genes in each of the comparisons. The results of this study should help in beginning to develop a molecular genomic approach for the diagnosis and treatment of different headache disorders.