The President Ramsay Award*

Relation of Endothelial Genes to Migraine and Stroke
Leah MacClellan
School of Medicine, University of Maryland, Baltimore

*Funded in part by a generous gift from the Office of the President, University of Maryland, Baltimore.

Approximately 9% of adult strokes in the US occur in those younger than 45 years of age, potentially leading to costly long-term disability or death. Although research of early-onset stroke could promote further understanding of the disorder and represents an opportunity for early risk-factor modification or intervention, this condition has received little attention from researchers. Like stroke, migraine is a complex neurological disorder that is associated with focal neurological deficits, alterations in cerebral blood flow, and headache. Migraine disproportionaly affects young women and is an independent predictor of ischemic stroke, specifically among young women. However, the mechanism by which migraine and stroke are associated remains unclear. Both disorders exhibit familial clustering, a finding that is consistent with shared enviromental risk factors and/or a genetic contribution.

Recent evidence suggests that genes regulating endothelial function are promising candidate genes for migraine and stroke susceptibility because of the importance of endothelial function in regulating vasoconstriction and vasodilation of blood vessels and cerebral blood flow. Selected variants of these genes have been studied in relation to migraine and stroke separately, however a systematic study has not been done to assess the interaction of gene variants with migraine as a risk factor for ischemic stroke. Using existing data from The Stroke Prevention in Young Women Study, a population-based case-control study of early onset-stroke, we propose to evaluate the association between migraine and stroke among 1,107 women age 15-49 years and whether polymorphisms in the NOS3, EDN1, EDNRA, and EDNRB genes may confer susceptibility to both conditions.