Angiotensinogen gene core promoter variants and non-modulating hypertension

Hilgers, K., Delles, C. , Veelken, R. and Schmieder, R. (2001) Angiotensinogen gene core promoter variants and non-modulating hypertension. Hypertension, 38(6), pp. 1250-1254. (doi: 10.1161/hy1201.096545)

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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.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Delles, Professor Christian
Authors: Hilgers, K., Delles, C., Veelken, R., and Schmieder, R.
College/School:College of Medical Veterinary and Life Sciences
College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:Hypertension
Publisher:American Heart Association

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