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Variation at the Aldosterone Synthase (CYP11B2) Locus Contributes to Hypertension in Subjects with a Raised Aldosterone-to-Renin Ratio

Hypertension Research Centre (P.O.L., T.M.M.), Directorate of Biochemical Medicine (E.Do.), Department of Endocrinology (R.T.J.), Ninewells Hospital and Medical School, Dundee DD1 9SY, United Kingdom; Medical Research Council Blood Pressure Group (C.H., E.F., N.H.A., E.Da., R.F., J.M.C.C.), Western Infirmary, Glasgow, G11 6NT, United Kingdom; and Department of Cardiology (P.O.L.), Wales Heart Research Institute, University of Wales College of Medicine, Heath Park, Cardiff, CF14 4XN, United Kingdom

Abstract

The aldosterone-to-renin ratio (ARR) is a marker of aldosterone activity in hypertension. We examined the relationship of the ARR to the distribution of two biallelic polymorphisms at the CYP11B2 gene locus. One polymorphism affects a putative steroidogenic factor-1 binding site (-344 T/C) in the 5'-regulatory region, whereas the other marker reflects replacement of the intron-2 from CYP11B2 with that from the neighboring gene encoding 11ß-hydroxylase (CYP11B1; wild-type/conversion). We studied consecutive referrals to the Tayside hypertension clinic in 1998. Because the specificity of ARR (pmol/liter/ng/ml/h) for hyperaldosteronism increases with its threshold, ARRs of at least 750 and 1000 were used. A total of 375 patients were assessed; 86.9% had complete data. There were significant excesses of steroidogenic factor-1 (T) (ARR 750, 0.62 vs. 0.51, P = 0.014; ARR 1000, 0.63 vs. 0.51, P = 0.039) and intron-2 (conversion) (ARR 750, 0.49 vs. 0.41, P = 0.205; ARR 1000, 0.54 vs. 0.41, P = 0.029) alleles in patients with a raised ARR. The odds ratio for a raised ARR was 2.27 [95% confidence interval, 1.01, 5.09; P < 0.05] comparing patients with a homozygous haplotype for these alleles with those without any such alleles, and this risk increased with age. This study supports the notion that there is a genetic component that regulates aldosterone production and that hyperaldosteronism might develop over time in susceptible individuals.

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