Several frequent polymorphisms in the CYP11B2 gene are suggested to be associated with essential hypertension and aldosterone secretion. In this study, we investigated the association of polymorphisms in CYP11B2 and CYP11B1 genes with the risk of primary hyperaldosteronism (PH). Three polymorphisms in the CYP11B2 gene (intron 2 conversion, rs1799998 and rs4539) and two polymorphisms in the CYP11B1 gene (rs6410 and rs6387) were analyzed in patients with PH and in the normal population. The rs6410 allelic frequencies in patients with aldosterone-producing adenoma (APA) and idiopathic hyperaldosteronism (IHA) were significantly different from those in controls at P = 1.09 x 10(-5) and 0.015, respectively. There was a relative excess of AA homozygotes and AG heterozygotes of the rs6410 allele in the APA group as compared with the control group (P = 2.19 x 10(-4)). There were significantly different genotypes, AA and AG, of the rs6410 allele between the patients with IHA and the controls only after adjustments for age, gender and body mass index (odds ratio (OR) 4.06, 95% confidence interval (CI) 1.31-12.66; OR 2.41, 95% CI 1.02-5.72). One susceptible haplotype, AAAWT, was identified to be significantly associated with APA (OR 1.44, 95% CI 1.19-1.76), and three susceptible haplotypes, AAAWT, AGGWT and AGAWC, were identified to be significantly associated with IHA (OR 1.55, 95% CI 1.23-1.96; OR 1.49, 95% CI 1.17-1.89; OR 1.40, 95% CI 1.04-1.88). In contrast, one protective haplotype, GGAWT, showed a significant difference between the patients with APA and controls (OR 0.73, 95% CI 0.55-0.97). Several haplotypes were associated with ARR in both the controls and cases. Our data demonstrated that there was a significant association between polymorphisms in the CYP11B2 and CYP11B1 genes and a genetic predisposition to PH. The association with IHA seemed closer compared with APA. Hypertension Research (2010) 33, 478-484; doi: 10.1038/hr.2010.21; published online 26 March 2010