This study focused on 3 genetic polymorphisms that have previously been implicated in hypertension: the α-adducin (ADD1/Gly460Trp), β1-adrenoreceptor (ADRB1/Arg389Gly), and G-protein β3 subunit (GNB3/C825T) gene polymorphisms. We determined genetic variants using the TaqMan system in a large cohort representing the general population in Japan (867 males, 1,013 females). Logistic analysis indicated that the ADD1/ G460W polymorphism was associated with hypertension in female subjects. The odds ratio of the WW genotype for hypertension was 1.53 (95%CI, 1.12-2.08) over the WG+GG genotype (p =0.0070, p corrected (p_c) =0.0420 corrected by the Bonferroni method). The ADRB1/R389G polymorphism tended to be associated with hypertensive status in male subjects (p =0.0117, p_c =0.0702). The odds ratio of the GG genotype for hypertension was 0.38 (95%CI, 0.167-0.780) over the RR+RG genotype. The GNB3/C825T polymorphism was not associated with hypertensive status in either male or female subjects. The present results do not agree with those in previous reports. Almost all common variants may have only a modest effect on common diseases, and a single study even employing 1,880 subjects may lack the statistical power to detect a real association. Accordingly, it will be necessary to verify the association between these three genes and hypertension using a larger number of subjects from the Suita cohort or another population. (Hypertens Res 2004; 27: 31-37)