ASSOCIATIONS BETWEEN ALDOSTERONE SYNTHASE GENE POLYMORPHISM AND THE ADRENOCORTICAL FUNCTION IN MALES

Objectives. Two diallelic polymorphisms, one in the transcriptional re gulatory region (promoter) and the other in the second intron, have be en identified in the aldosterone synthase (CYP11B2) gene encoding aldo sterone synthase, the enzyme catalysing the last steps of aldosterone biosynthesis. We have examined the associations between these genetic variations and adrenocortical function in a cohort of Finnish males. D esign. A cross-sectional study. Setting. Helsinki University Central H ospital, Finland. Subjects. Ninety-two males aged 30-55 years. Main ou tcome measures. Basal adrenocortical function was assessed by measurin g urinary excretion of aldosterone and cortisol. Functional activity w as determined by responses of several adrenal steroids to dexamethason e suppression followed by ACTH stimulation. Polymerase chain reactions were used to identify the polymorphisms in the CYP11B2 gene. Results. The -344TT genotype group in the CYP11B2 promoter had lower systolic blood pressures (P = 0.039), but higher urinary aldosterone excretion (P = 0.016), and 11-deoxycortisol responses to ACTH stimulation (P = 0 .021) than the -344CC genotype group. Urinary aldosterone excretion (P = 0.033), 11-deoxycortisol (P = 0.026), and aldosterone (P = 0.013) r esponses to ACTH were higher in the intron 2 conversion than the nonco nversion genotype groups. Conclusions. Polymorphisms in or near the al dosterone synthase gene are associated with variations in aldosterone and 11-deoxycortisol production in males. This may modulate the activi ty of the renin-angiotensin system and thereby contribute to blood pre ssure regulation.