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(Hypertension. 2001;38:1250.)
© 2001 American Heart Association, Inc.

Scientific Contributions

Angiotensinogen Gene Core Promoter Variants and Non-Modulating Hypertension

Karl F. Hilgers; Christian Delles; Roland Veelken; Roland E. Schmieder

Department of Medicine/Nephrology, University of Erlangen-Nürnberg, Nürnberg, Germany.

Correspondence to Prof Dr Roland E. Schmieder, Medizinische Klinik IV der Universität Erlangen-Nürnberg, Breslauer Strasse 201, D-90471 Nürnberg, Germany. E-mail Roland.Schmieder{at}rzmail.uni-erlangen.de

Non-modulation has been suggested as a possible intermediate phenotype defining a subgroup of genetic hypertension. The trait is characterized by an attenuated response of renal blood flow and/or aldosterone to angiotensin (Ang) II. We tested the hypothesis that functional polymorphisms of the core promoter of the angiotensinogen gene are associated with non-modulation. Fifty-six young, white, male, untreated hypertensive patients and 65 age-matched normotensive volunteers were genotyped for 3 known functional variants of the angiotensinogen core promoter. All subjects were infused with 2 doses (0.5 and 3 ng/kg per minute) of Ang II while they were on a high sodium diet (250 mmol/d). The blood pressure, renal plasma flow, and aldosterone responses to Ang II were not affected by the -6 G/A polymorphism. The -20 A/C variant had no significant effects on the blood pressure or renal hemodynamic response to Ang II. However, the aldosterone response to both doses of Ang II was significantly decreased in -20 C allele carriers compared with -20 AA homozygotes in a multivariate analysis. The -18 T allele was not detected in our population, and there was a linkage dysequilibrium between -20 C and -6 A: -20 C almost exclusively occurred on the -6 A allele. Haplotype analysis indicated that the -20 C/-6 A haplotype but not the -20 A/-6 A haplotype was associated with a decreased aldosterone response to Ang II. We conclude that the -20 C variant or the -20 C/-6 A haplotype of the angiotensinogen core promoter is associated with a blunted aldosterone response to Ang II and may thus contribute to the non-modulating phenotype.

Key Words: angiotensin • angiotensinogen • aldosterone • hypertension, non-modulating

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