Relation of candidate genes that encode for endothelial function to migraine and stroke: the Stroke Prevention in Young Women study.
OBJECTIVE
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.
MacClellan
Leah R
LR
Department of Epidemiology and Preventive Medicine, University of Maryland School of Medicine, Baltimore, MD 21201-1559, USA.
Howard
Timothy D
TD
Cole
John W
JW
Stine
O Colin
OC
Giles
Wayne H
WH
O'Connell
Jeffery R
JR
Wozniak
Marcella A
MA
Stern
Barney J
BJ
Mitchell
Braxton D
BD
Kittner
Steven J
SJ
D000293:Adolescent; D000328:Adult; D044383:Black People / Q000235:genetics; D016022:Case-Control Studies; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D019332:Endothelin-1 / Q000235:genetics*; D004730:Endothelium, Vascular / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D008881:Migraine Disorders / Q000208:ethnology / Q000235:genetics*; D009154:Mutation / Q000235:genetics; D052250:Nitric Oxide Synthase Type III / Q000235:genetics; D011110:Polymorphism, Genetic / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D044023:Receptor, Endothelin B / Q000235:genetics*; D020521:Stroke / Q000208:ethnology / Q000235:genetics*; D044465:White People / Q000235:genetics; D055815:Young Adult
D019332:Endothelin-1; D044023:Receptor, Endothelin B; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III