title: Variation at the aldosterone synthase (CYP11B2) locus contributes to hypertension in subjects with a raised aldosterone-to-renin ratio.
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 11beta-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.
authors.affiliation: Hypertension Research Centre, Ninewells Hospital and Medical School, Dundee DD1 9SY, United Kingdom. limpo@cf.ac.uk
authors.forename: Pitt O
authors.initials: PO
authors.lastname: Lim
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Macdonald
authors.forename: Christine
authors.initials: C
authors.lastname: Holloway
authors.forename: Elaine
authors.initials: E
authors.lastname: Friel
authors.forename: Niall H
authors.initials: NH
authors.lastname: Anderson
authors.forename: Eleanor
authors.initials: E
authors.lastname: Dow
authors.forename: Roland T
authors.initials: RT
authors.lastname: Jung
authors.forename: Eleanor
authors.initials: E
authors.lastname: Davies
authors.forename: Robert
authors.initials: R
authors.lastname: Fraser
authors.forename: John M C
authors.initials: JM
authors.lastname: Connell
mesh_terms: D000450:Aldosterone / Q000097:blood*; D001483:Base Sequence; D001794:Blood Pressure; D003404:Creatinine / Q000097:blood; D019405:Cytochrome P-450 CYP11B2 / Q000235:genetics*; D017931:DNA Primers; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000201:enzymology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011188:Potassium / Q000097:blood; D012083:Renin / Q000097:blood*; D012964:Sodium / Q000097:blood
chemical_list: D017931:DNA Primers; D000450:Aldosterone; D012964:Sodium; D003404:Creatinine; D019405:Cytochrome P-450 CYP11B2; D012083:Renin; D011188:Potassium