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(Stroke. 2009;40:e550.)
© 2009 American Heart Association, Inc.

Original Contributions

Relation of Candidate Genes that Encode for Endothelial Function to Migraine and Stroke

The Stroke Prevention in Young Women Study

Leah R. MacClellan, PhD; Timothy D. Howard, PhD; John W. Cole, MD; O. Colin Stine, PhD; Wayne H. Giles, MD; Jeffery R. O'Connell, PhD; Marcella A. Wozniak, MD; Barney J. Stern, MD; Braxton D. Mitchell, PhD Steven J. Kittner, MD

From Department of Epidemiology and Preventive Medicine (L.R.M., O.C.S., B.D.M.), Department of Medicine (J.R.O., B.D.M.), Department of Neurology (J.W.C., M.A.W., B.J.S., S.J.K.), University of Maryland School of Medicine, Baltimore, Md; Wake Forest University School of Medicine (T.D.H.), Winston-Salem, NC; VA Maryland Health Care System (J.W.C., M.A.W., B.J.S., S.J.K.), Baltimore, Md; Centers for Disease Control and Prevention (W.H.G.), Atlanta, Ga.

Correspondence to John W. Cole, MD, MS, Associate Professor, Maryland Stroke Center, Department of Neurology, University of Maryland School of Medicine, 12th Floor, Bressler Building, Room 12-006, 655 West Baltimore Street, Baltimore, MD 21201-1559. E-mail jcole{at}som.umaryland.edu

Background and Purpose— Migraine with aura is a risk factor for ischemic stroke, but the mechanism by which these disorders are associated remains unclear. Both disorders exhibit familial clustering, which may imply a genetic influence on migraine and stroke risk. Genes encoding for endothelial function are promising candidate genes for migraine and stroke susceptibility because of the importance of endothelial function in regulating vascular tone and cerebral blood flow.

Methods— Using data from the Stroke Prevention in Young Women study, a population-based case-control study including 297 women aged 15 to 49 years with ischemic stroke and 422 women without stroke, we evaluated whether polymorphisms in genes regulating endothelial function, including endothelin-1 (EDN), endothelin receptor type B (EDNRB), and nitric oxide synthase-3 (NOS3), confer susceptibility to migraine and stroke.

Results— EDN SNP rs1800542 and rs10478723 were associated with increased stroke susceptibility in whites (OR, 2.1; 95% CI, 1.1–4.2 and OR, 2.2; 95% CI, 1.1–4.4; P=0.02 and 0.02, respectively), as were EDNRB SNP rs4885493 and rs10507875, (OR, 1.7; 95% CI, 1.1–2.7 and OR, 2.4; 95% CI, 1.4–4.3; P=0.01 and 0.002, respectively). Only 1 of the tested SNP (NOS3 rs3918166) was associated with both migraine and stroke.

Conclusions— In our study population, variants in EDN and EDNRB were associated with stroke susceptibility in white but not in black women. We found no evidence that these genes mediate the association between migraine and stroke.

Key Words: endothelium • ischemia • migraine • stroke in young adults