Genome-wide association studies have identified several polymorphisms that appear to be on hypertension-susceptible regions. We performed the current replication study in order to evaluate the association of these loci with hypertension in healthy Japanese males and then examined the combined effect of 12 independent variants. Overall, 735 Japanese men from two independent cohorts were recruited. Association with hypertension was assessed in 16 polymorphisms on 12 genes and 12 were chosen to evaluate the combined impact. Polymorphisms on the COMT, ATP2B1, CYP11A1 and the CSK genes were confirmed to be associated with hypertension and blood pressure (BP). Current findings also replicated previous results for the CYP11B2 and PTGIS genes. Although there were no significant associations found for other variants, our results suggested there was a combined impact for 12 loci. Individuals carrying more risk alleles had a higher risk of hypertension (P for the slope=0.002). Blood pressures also increased in conjunction with an increasing risk allele score (P for trend=7.84 × 10(-6) and 1.85 × 10(-5) for SBP and DBP, respectively). Our results confirmed the associations between hypertension or blood pressure and four gene variants. We also found a significant combined effect of the 12 gene loci.