Variation at the aldosterone synthase (CYP11B2) locus contributes to hypertension in subjects with a raised aldosterone-to-renin ratio

TY - JOUR

T1 - Variation at the aldosterone synthase (CYP11B2) locus contributes to hypertension in subjects with a raised aldosterone-to-renin ratio

AU - Lim, Pitt O.

AU - Macdonald, Thomas M.

AU - Holloway, Christine

AU - Friel, Elaine

AU - Anderson, Niall H.

AU - Dow, Eleanor

AU - Jung, Roland T.

AU - Davies, Eleanor

AU - Fraser, Robert

AU - Connell, John M.C.

PY - 2002/9/1

Y1 - 2002/9/1

N2 - 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 11β-hydroxylase (CYP11B1; wildtype/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.

AB - 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 11β-hydroxylase (CYP11B1; wildtype/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.

UR - https://www.scopus.com/pages/publications/18544362070

U2 - 10.1210/jc.2001-012070

DO - 10.1210/jc.2001-012070

M3 - Article

C2 - 12213905

AN - SCOPUS:18544362070

SN - 0021-972X

VL - 87

SP - 4398

EP - 4402

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

IS - 9

ER -