Significant linkage and association of alpha-adducin, a cytoskeleton protein involved in transmembrane ion transport, with essential hypertension were recently shown in Caucasian populations, especially in relation to salt sensitivity. The present study investigated the relevance of this candidate gene to hypertension in a well-characterized Japanese population. A total number of 507 individuals were selected from clinic outpatients. Hypertensive subjects were defined on the basis of the individual's blood pressure readings before starting medications; the criteria included systolic blood pressure > or = 160 mm Hg and/or diastolic blood pressure > or = 95 mm Hg. Patients with diabetes mellitus, renal failure, and secondary forms of hypertension had been excluded. Control subjects had blood pressure values < 130/85 mm Hg. The allele frequency of a genetic variant at amino acid residue 460 of alpha-adducin (460Trp) was compared between cases and control subjects with chi(2) statistics; in addition, the association was tested with blood pressure as a continuous variable. No significant association was found in either of the statistics tested. The 460Trp variant appeared to be relatively common in the Japanese (54% to 60%) compared with a reported prevalence of 13% to 23% in Caucasians. The present study brought up an important issue concerning the pathophysiological role of alpha-adducin in non-Caucasian populations, given the likely ethnic variation in the nature of genetic susceptibility loci. The 460Trp variant of the alpha-adducin gene is unlikely to have a major effect on susceptibility to hypertension in the Japanese population studied, although the present study does not exclude the involvement of alpha-adducin in the pathogenesis of hypertension.