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A Biallelic Gene Polymorphism of CYP11B2 Predicts Increased Aldosterone to Renin Ratio in Selected Hypertensive Patients

Division of Nephrology and Hypertension, Inselspital, University of Berne, 3010 Berne, Switzerland

Address all correspondence and requests for reprints to: Paolo Ferrari, M.D., Department of Nephrology, Fremantle Hospital, University of Western Australia, Alma Street, P.O. Box 480, Fremantle WA 6959 Australia. E-mail: paolo.ferrari{at}health.wa.gov.au.

Altered control of aldosterone synthase (CYP11B2) gene expression may modulate aldosterone secretion, as suggested by a raised aldosterone to renin ratio (ARR) in some patients with essential hypertension.

We compared the frequency of two linked CYP11B2 polymorphisms, one in the steroidogenic factor-1 (SF-1) binding site and the other an intronic conversion (Int2) in relation to ARR in 141 hypertensive patients. Patients were divided into groups with either normal or high supine ARR using a cut-off threshold of 145 pmol/liter per ng/liter. Supine ARR was normal in 104 patients and raised in 37 patients. The two polymorphisms were in strong linkage disequilibrium (² = 123.8; P < 0.0001). The SF-1 T and Int2 C alleles were more prevalent among patients with high ARR (46% and 43%, respectively) than with normal ARR (22% and 17%; P < 0.01 and P < 0.005, respectively). Odds ratios for raised ARR in subjects with a homozygous SF-1 T and Int2 C haplotype were 6.1 (95% confidence interval, 1.6–22.5; P < 0.005) when compared with the contrasting haplotype. Linear modeling of individual postural changes in renin and aldosterone showed a maximal achievable aldosterone increase of 110 pmol/liter with no mutated haplotype and 500 pmol/liter with two mutated haplotypes. These findings support the view of a molecular basis regulating aldosterone production.

This work was supported in part by a grant from the Swiss National Research Foundation (3100-58889) and the Cloëtta Foundation, Zurich, Switzerland.

Abbreviations: Aldo_max, Maximal achievable aldosterone increase; ARR, aldosterone to renin ratio; CI, confidence interval; Int2, intronic conversion; irR, immunoreactive renin; SF-1, steroidogenic factor-1.

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