(Stroke. 2001;32:822.)
© 2001 American Heart Association, Inc.
Original Contributions |
G-Protein ß3 Subunit and 
-Adducin Polymorphisms and Risk of Subclinical and Clinical Stroke
From the Human Genetics Center, University of Texas–Houston Health Science Center, (A.C.M, E.B.); Institute of Molecular Medicine, Houston, Tex (P.A.D., E.B.); University of Minnesota, School of Public Health, Division of Epidemiology, Minneapolis (A.R.F.); and Johns Hopkins University, School of Hygiene and Public Health, Baltimore, Md (F.J.N.).
Correspondence to Eric Boerwinkle, PhD, Human Genetics Center and Institute of Molecular Medicine, University of Texas–Houston Health Science Center, 6901 Bertner, Houston, TX 77030. E-mail eboerwin{at}gsbs.gs.uth.tmc.edu
Background
and Purpose—Essential hypertension is a
significant risk factor for stroke. Genes contributing to
interindividual variation in blood pressure levels and essential
hypertension status may play a role in the etiology of stroke either
through their effects on blood pressure levels or through separate
pathways. For this reason, we sought to examine the association between
the 
-adducin (ADD1) G/W460
and G-protein ß3 subunit
(GNß3) 825C/T
polymorphisms and subclinical and clinical stroke in the
Atherosclerosis Risk in Communities (ARIC)
Study.
Methods—Subclinical stroke was determined by cerebral MRI. Subclinical cerebral infarct cases (n=202) were compared with a stratified random sample (MRI-CRS) identified from individuals participating in the MRI examination (n=211). Incidence of clinical ischemic stroke was determined by following the ARIC cohort for an average of 7.2 years for potential cerebrovascular events; 231 validated clinical ischemic strokes were identified. A stratified random sample of the ARIC cohort (CRS) (n=984) was used as the comparison group for the clinical cases.
Results—The frequency of the ADD1 W460 allele was determined for the subclinical cases (0.12), MRI-CRS (0.16), clinical cases (0.14), and CRS (0.17). The frequency of the GNß3 825T allele was determined in whites and blacks, respectively, for the subclinical cases (0.26, 0.73), MRI-CRS (0.31, 0.75), clinical cases (0.36, 0.72), and CRS (0.30, 0.72). The ADD1 W460 and GNß3 825T alleles were not significantly associated with subclinical stroke. The ADD1 W460 allele was also not a significant predictor of clinical stroke. The GNß3 825T allele was significantly associated with clinical stroke in whites after adjustment for age and sex (hazard rate ratio, 1.45; 95% CI, 1.05 to 2.00) and after further adjustment for multiple stroke risk factors (hazard rate ratio, 1.68; 95% CI, 1.18 to 2.41). The GNß3 825T allele was not significantly associated with clinical stroke in blacks for either adjustment model.
Conclusions—The GNß3 gene 825C/T polymorphism is significantly associated with incident clinical ischemic stroke in a white middle-aged American population, but not in blacks. This association does not appear to be mediated by established stroke risk factors, specifically blood pressure levels or hypertension status.
Editorial Comment
Candidate Genes for Stroke: If Elected, Will They Serve?
Blackburn Cardiovascular Genetics Laboratory, Robarts Research Institute, London, Ontario, Canada
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