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
2002 (English)In: Journal of Hypertension, ISSN 0263-6352, E-ISSN 1473-5598, Vol. 20, no 4, 657-663 p.Article in journal (Refereed) Published
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.
Place, publisher, year, edition, pages
2002. Vol. 20, no 4, 657-663 p.
Aged, Alleles, 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, Male, Middle Aged, Polymorphism; Genetic, Receptor; Angiotensin; Type 1, Receptors; Angiotensin/antagonists & inhibitors/*genetics, Renin-Angiotensin System/genetics, Research Support; Non-U.S. Gov't, Sweden, Tetrazoles/*therapeutic use
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-73090PubMedID: 11910301OAI: oai:DiVA.org:uu-73090DiVA: diva2:101001