Recently, a molecular variant of alpha-adducin (with tryptophan instead of glycine at amino acid number 460) has been reported to be more common among Italian and French hypertensive individuals than among controls. Moreover, hypertensive individuals with Trp460 exhibit a greater sensitivity to changes in sodium balance and a greater fall in blood pressure in response to diuretic treatment. In the present study, we investigated the association between Gly460Trp polymorphism of the alpha-adducin gene and hypertension in Japanese subjects. The study population comprised 283 subjects enrolled at our outpatient clinic. The subjects were divided into normotensive (NT), borderline (B), and hypertensive (HT) groups. The alpha-adducin genotype was determined by allele-specific oligonucleotide hybridization. The genotype frequency of Gly460Trp polymorphism differed significantly among the NT, B, and HT groups (p=0.0113). The GG genotype of the adducin gene was more common in the NT group than in the HT group. Moreover, the Trp460 allele was significantly associated with lower plasma renin activity (p = 0.0075). However, this polymorphism was unrelated to left ventricular mass and height as assessed by echocardiography. The present study suggests that Gly460Trp polymorphism of the a-adducin gene may be involved in hypertension, particularly the low-renin type, in Japanese individuals.