Polymorphisms in the angiotensinogen and angiotensin II type 1 receptor gene are related to change in left ventricular mass during antihypertensive treatment: results from the Swedish Irbesartan Left Ventricular Hypertrophy Investigation versus Atenolol (SILVHIA) trial.

Abstract

BACKGROUND:

Our aim was to determine if gene polymorphisms in the renin-angiotensin-aldosterone system (RAAS) were related to the degree of change in left ventricular hypertrophy (LVH) during antihypertensive treatment.

METHODS AND RESULTS:

Patients with essential hypertension and echocardiographically diagnosed LVH were included in a double-blind study to receive treatment with either the angiotensin II type 1 receptor (AT1-receptor) antagonist irbesartan (n = 41), or the beta-1 adrenergic receptor blocker atenolol (n = 43) as monotherapy for 3 months. The angiotensinogen T174M and M235T, the angiotensin-converting enzyme I/D, the AT1-receptor A1166C and the aldosterone synthase (CYP11B2) -344 C/T polymorphisms were analysed and related to the change in left ventricular mass (LVM). Patients with the angiotensinogen 174 TM genotype treated with irbesartan responded with the greatest reduction in LVM (-23 +/- 31SD g/m2 for TM and +0.5 +/- 18 g/m2 for TT, P = 0.005), independent of blood pressure reduction. Both the angiotensinogen 235 T-allele (P = 0.02) and the AT1-receptor 1166 AC genotype responded with the greatest reduction in LVM when treated with irbesartan (-0.1 +/- 19 g/m2 for AA and -18 +/- 30 g/m2 for AC, P = 0.02), independent of blood pressure reduction. These polymorphisms were not associated with the change in LVM during treatment with atenolol.

DISCUSSION:

The angiotensinogen T174M and M235T and the AT1-receptor A1166C polymorphisms were related to the change in LVH during antihypertensive treatment with an AT1-receptor antagonist; of these angiotensinogen T174M was the most powerful. This highlights the role of the RAAS for left ventricular hypertrophy and the potential of pharmacogenetics as a tool for guidance of antihypertensive therapy.

• Authors: Lisa Kurland, Håkan Melhus, Julia Karlsson, Thomas Kahan, Karin Malmqvist, Peter Ohman, Fredrik Nyström, Anders Hägg, Lars Lind
• Journal: Journal of hypertension (J Hypertens) Vol. 20 Issue 4 Pg. 657-63 (Apr 2002) ISSN: 0263-6352 [Print] England
• PMID: 11910301 (Publication Type: Clinical Trial, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Angiotensin Receptor Antagonists
• Antihypertensive Agents
• Biphenyl Compounds
• Receptor, Angiotensin, Type 1
• Receptors, Angiotensin
• Tetrazoles
• Angiotensinogen
• Atenolol
• Irbesartan

Topics

• Aged
• Alleles
• Angiotensin Receptor Antagonists
• Angiotensinogen (genetics)
• Antihypertensive Agents (therapeutic use)
• Atenolol (therapeutic use)
• Biphenyl Compounds (therapeutic use)
• Female
• Humans
• Hypertension (drug therapy, genetics, pathology)
• Hypertrophy, Left Ventricular (drug therapy, genetics, pathology)
• Irbesartan
• Male
• Middle Aged
• Polymorphism, Genetic
• Receptor, Angiotensin, Type 1
• Receptors, Angiotensin (genetics)
• Renin-Angiotensin System (genetics)
• Sweden
• Tetrazoles (therapeutic use)