G-protein beta 3 subunit and alpha-adducin polymorphisms and risk of subclinical and clinical stroke

Background and Purpose-Essential hypertension is a significant risk factor for stroke. Genes contributing to interindividual variation in blood pressu re 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 b etween the alpha -adducin (ADD1) G/W460 and G-protein beta3 subunit (GN bet a3) 825C/T polymorphisms and subclinical and clinical stroke in the Atheros clerosis Risk in Communities (ARIC) Study. Methods-Subclinical stroke was determined by cerebral MRI. Subclinical cere bral 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 followin g the ARIC cohort for an average of 7.2 years for potential cerebrovascular events; 231 validated clinical ischemic strokes were identified. A stratif ied random sample of the ARIC cohort (CRS) (n = 983) was used as the compar ison group for the clinical cases. Results-The frequency of the ADD1 W460 allele was determined for the subcli nical cases (0.12), MRI-CRS (0.16), clinical cases (0.14), and CRS (0.17). The frequency of the GN beta3 825T allele was determined in whites and blac ks, 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 G N beta3 825T alleles were not significantly associated with subclinical str oke. The ADD1 W460 allele was also not a significant predictor of clinical stroke. The GN beta3 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 ri sk factors (hazard rate ratio, 1.68; 95% CI, 1.18 to 2.41). The GN beta3 82 5T allele was not significantly associated with clinical stroke in blacks f or either adjustment model. Conclusions-The GN beta3 gene 825C/T polymorphism is significantly associat ed with incident clinical ischemic stroke in a white middle-aged American p opulation, but not in blacks. This association does not appear to be mediat ed by established stroke risk factors, specifically blood pressure levels o r hypertension status.