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(Hypertension. 2001;38:1204.)
© 2001 American Heart Association, Inc.

Fourth International Seminar on Cardiovascular Biology and Medicine: Part I

Molecular Basis of Salt Sensitivity in Human Hypertension

Evaluation of Renin-Angiotensin-Aldosterone System Gene Polymorphisms

Esteban Poch; Daniel González; Vicente Giner; Ernesto Bragulat; Antonio Coca; Alejandro de la Sierra

From the Nephrology Department (E.P., D.G.) and Hypertension Unit, Department of Internal Medicine (V.G., E.B., A.C., A.d.l.S.), IDIBAPS (Institut d’Investigacions Biomèdiques August Pi I Sunyer), Hospital Clínic, University of Barcelona, Spain.

Correspondence to Esteban Poch, MD PhD, Nephrology Service, Hospital Clínic, Villarroel 170, 08036, Barcelona. Spain. E-mail epoch{at}medicina.ub.es

Abstract

Abstract—— We analyzed the association between salt sensitivity in essential hypertension and 8 genetic polymorphisms in 6 genes of the renin-angiotensin aldosterone system. Seventy-one patients with essential hypertension were classified as salt sensitive or salt resistant by means of the 24-hour ambulatory blood pressure (BP) change to high salt intake. The polymorphisms evaluated correspond to the following genes: ACE (I/D), angiotensinogen (M235T), angiotensin II type 1 receptor (A1166C), 11ß-Hydroxysteroid dehydrogenase type 2 (11ßHSD2) (G534A), aldosterone synthase (C-344T and Intron 2 conversion), and the mineralocorticoid receptor (G3514C and A4582C); all were determined using standard polymerase chain reaction methods. Thirty-five patients (49%) were classified as salt sensitive. We analyzed the BP response to high salt intake among genotypes and found a significant association for ACE I/D and 11ßHSD2 G534A polymorphisms. Patients homozygous for the insertion allele of the ACE gene (II) had a significantly higher BP increase with high salt intake than did patients homozygous for the deletion allele (DD). Heterozygous patients (ID) exhibited an intermediate response. The prevalence of salt-sensitive hypertension was also significantly higher (P=0.003) in II (68%) and DI patients (59%) compared with DD hypertensives (19%). With respect to 11ßHSD2 G534A, patients with the GG genotype had a significantly higher systolic BP increase with high salt intake than did GA patients. In addition, plasma renin activity suppression in response to high salt was significantly greater in GA patients than in GG patients. The prevalence of salt-sensitive hypertension was 14.3% in GA patients and 50.8% in GG patients (P=0.067). In conclusion, the I allele of ACE I/D polymorphism is significantly associated to salt-sensitive hypertension. The BP response to high salt intake was different among genotypes of ACE I/D and 11ßHSD G534A, suggesting that these polymorphisms may be potentially useful genetic markers of salt sensitivity.

Key Words: angiotensin-converting enzyme • angiotensinogen • receptors, angiotensin • mineralocorticoids • aldosterone • genes • polymorphism • sodium

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