Associations between aldosterone synthase gene polymorphism and the adrenocortical function in males

Abstract . Hautanen A, Lankinen L, Kupari M, Jänne OA, Adlercreutz H, Nikkilä H, White PC (Helsinki University Central Hospital and University of Helsinki, Helsinki, Finland. University of Texas Southwestern Medical Center, Dallas, TX, USA). Associations between aldosterone synthase gene polymorphism and the adrenocortical function in males. J Intern Med 1998; 244 : 11–18. Objectives Two diallelic polymorphisms, one in the transcriptional regulatory region (promoter) and the other in the second intron, have been identified in the aldosterone synthase (CYP11B2) gene encoding aldosterone 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. Design A cross‐sectional study. Setting Helsinki University Central Hospital, Finland. Subjects Ninety‐two males aged 30–55 years. Main outcome measures Basal adrenocortical function was assessed by measuring urinary excretion of aldosterone and cortisol. Functional activity was determined by responses of several adrenal steroids to dexamethasone 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) responses to ACTH were higher in the intron 2 conversion than the nonconversion genotype groups. Conclusions Polymorphisms in or near the aldosterone synthase gene are associated with variations in aldosterone and 11‐deoxycortisol production in males. This may modulate the activity of the renin–angiotensin system and thereby contribute to blood pressure regulation.