Genomics of Pediatric Headache Disorders

小儿头痛疾病的基因组学

• 批准号: 6916529
• 负责人: ANDREW D HERSHEY
• 金额: $ 31.01万
• 依托单位: CINCINNATI CHILDRENS HOSP MED CTR
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-07-15 至 2007-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6916529
• 关键词: RNA; adolescence (12-20); blood chemistry; clinical research; functional /structural genomics; gene expression; genetic susceptibility; headache; human subject; microarray technology; middle childhood (6-11); migraine; nonsteroidal antiinflammatory agent; patient oriented research; pediatrics; pharmacogenetics; polymerase chain reaction

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.

描述（由申请人提供）：该项目将检查偏头痛患者血液中的基因表达。我们已经使用微阵列显示，在缺血、出血、癫痫持续状态和胰岛素诱导的低血糖大鼠中存在独特的血液基因组谱。最近的人类研究结果表明，性别和年龄对血液基因组表达有深远的影响，Y染色体上的基因将男性与女性血液样本区分开来，淋巴细胞特异性基因随着年龄的增长而减少。 我们还发现了1型神经纤维瘤病（一种常染色体显性遗传疾病）的特异性血液基因组图谱。我们假设偏头痛，一种非孟德尔遗传性疾病，将有一个特定的血液基因组图谱。事实上，我们的初步数据表明，患有急性发作性偏头痛的儿童和患有慢性日常头痛的儿童具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儿童或健康对照儿童不同。该提案旨在确认这些初步发现，并确定急性偏头痛和慢性每日头痛患者是否具有相似或不同的血液基因组谱，以及与需要曲坦类作为急救药物的患者相比，对NSAID（非甾体抗炎药）有反应的患者是否具有不同的血液基因组谱。该研究涉及在头痛期间和头痛无间隔期间（内部对照）从偏头痛和慢性每日头痛患者中采集血液样本，并将这些样本与没有偏头痛或偏头痛家族史的对照患者进行比较。将来自全血的RNA分离、标记并应用于调查大部分人类基因组的人类寡核苷酸微阵列。最近开发的统计程序被用来确定潜在的转录调节头痛相比，控制患者。将使用定量的真实的时间RT-PCR来确认每次比较中的这些调节基因。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。