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(Hypertension. 2000;35:512.)
© 2000 American Heart Association, Inc.

Scientific Contributions

Renin-Angiotensin System Genetic Polymorphisms and Salt Sensitivity in Essential Hypertension

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

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

Correspondence to Alejandro de la Sierra, MD, Hypertension Unit, Department of Internal Medicine, Hospital Clínic, Villarroel 170, 08036, Barcelona, Spain. E-mail iserte{at}medicina.ub.es

Abstract—We evaluated the association between salt-sensitive hypertension and 3 different genetic polymorphisms of the renin-angiotensin system. Fifty patients with essential hypertension were classified as salt sensitive or salt resistant, depending on the presence or absence of a significant increase (P<0.05) in 24-hour ambulatory mean blood pressure (BP) after high salt intake. The insertion/deletion (I/D) angiotensin-converting enzyme (ACE) gene, the M235T angiotensinogen (AGT) gene, and the A1166C angiotensin II type 1 (AT1) receptor gene polymorphisms were determined with the use of standard polymerase chain reaction methods. Twenty-four (48%) patients with significantly increased (P<0.05) 24-hour mean BP with high salt intake (from 107.3±9.4 to 114.8±10.6 mm Hg) were classified as salt sensitive. In the remaining 26 patients (52%), high salt intake did not significantly modify 24-hour mean BP (from 107.6±10 to 107.8±9 mm Hg), and they were classified as having salt-resistant hypertension. We did not find any significant association between either M235T AGT or A1166C AT1 receptor genotypes and the BP response to high salt intake. However, patients with essential hypertension homozygous for the insertion allele of the ACE gene (II) had a significantly higher BP increase with high salt intake (9.8±8.1 mm Hg for systolic BP and 5.2±4.2 mm Hg for diastolic BP) than that observed in patients homozygous for the deletion allele (DD) (1.2±5.9 mm Hg for systolic BP; P=0.0118 and -0.2±4.2 mm Hg for diastolic BP; P=0.0274). Heterozygous patients (ID) exhibited an intermediate response. The prevalence of salt-sensitive hypertension also was significantly higher (P=0.012) in II (67%) and DI patients (62%) compared with DD hypertensives (19%). We conclude that a significant association exists between the I/D polymorphism of the ACE gene and salt-sensitive hypertension. Patients with II and DI genotypes have significantly higher prevalence of salt sensitivity than DD hypertensives.

Key Words: angiotensin-converting enzyme • genes • angiotensin II • blood pressure monitoring, ambulatory

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