Genomics of Pediatric Headache Disorders

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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.