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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS045752-02
Application #
6772497
Study Section
Special Emphasis Panel (ZRG1-BDCN-5 (01))
Program Officer
Porter, Linda L
Project Start
2003-07-15
Project End
2007-06-30
Budget Start
2004-07-01
Budget End
2005-06-30
Support Year
2
Fiscal Year
2004
Total Cost
$313,651
Indirect Cost
Name
Cincinnati Children's Hospital Medical Center
Department
Type
DUNS #
071284913
City
Cincinnati
State
OH
Country
United States
Zip Code
45229
Hershey, Andrew; Horn, Paul; Kabbouche, Marielle et al. (2012) Genomic expression patterns in menstrual-related migraine in adolescents. Headache 52:68-79
Hershey, Andrew D; Burdine, Danny; Kabbouche, Marielle A et al. (2011) Genomic expression patterns in medication overuse headaches. Cephalalgia 31:161-71
Hershey, Andrew D; Lipton, Richard B (2010) Lifestyles of the young and migrainous. Neurology 75:680-1
Mack, Kenneth J; Hershey, Andrew D (2009) Chronic daily headache in adolescence: a continuing problem. Neurology 73:412-3
Hershey, A D; Burdine, D; Liu, C et al. (2008) Assessing quality and normalization of microarrays: case studies using neurological genomic data. Acta Neurol Scand 118:29-41
Tang, Yang; Gilbert, Donald L; Glauser, Tracy A et al. (2005) Blood gene expression profiling of neurologic diseases: a pilot microarray study. Arch Neurol 62:210-5
Hershey, Andrew D; Winner, Paul; Kabbouche, Marielle A et al. (2005) Use of the ICHD-II criteria in the diagnosis of pediatric migraine. Headache 45:1288-97
Hershey, Andrew D; Tang, Yang; Powers, Scott W et al. (2004) Genomic abnormalities in patients with migraine and chronic migraine: preliminary blood gene expression suggests platelet abnormalities. Headache 44:994-1004
Tang, Yang; Schapiro, Mark B; Franz, David N et al. (2004) Blood expression profiles for tuberous sclerosis complex 2, neurofibromatosis type 1, and Down's syndrome. Ann Neurol 56:808-14