CYP11B2 gene polymorphisms in idiopathic hyperaldosteronism

Primary aldosteronism is characterized by autonomous production of aldoster one and arterial hypertension, and it occurs in 2 principal forms: aldoster one-producing adenoma (APA) and idiopathic hyperaldosteronism (IHA). APA ca n be cured through removal of the adenoma, whereas IHA leads to hypertensio n that must be treated with medication. The origin of the autonomous aldost erone production in IHA is poorly understood, but genetic factors may contr ibute to its cause. To test the hypothesis that variants of the aldosterone synthase gene may contribute to susceptibility to IHA, we compared genotyp es at 3 polymorphic sites in the CYP11B2 gene in patients with IHA (n=90) w ith those found in patients with APA (n=38), in patients with essential hyp ertension (n=72), and in normotensive individuals (n=102). We observed sign ificant linkage disequilibrium among the 3 polymorphisms with 2 frequent ha plotypes in all groups studied. One haplotype (C2R) was found to be increas ed in frequency in the IHA group (47%) compared with the other groups, whic h had a similar haplotype frequency (36%). The 3 polymorphisms studied have been implicated in either essential hypertension or excess aldosterone pro duction in previous studies. Because of the strong linkage disequilibrium, the observed results could be due to the action of any 1 of the 3 alleles o r to another allele in linkage disequilibrium with them. Our results sugges t that variations in the CYP11B2 gene may contribute to dysregulation of al dosterone synthesis and lead to susceptibility to IHA.