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.
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.


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.


CONCLUSIONS
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.
Kurland
Lisa
L
Department of Internal Medicine, Uppsala University Hospital, Uppsala, Sweden. lisa.kurland@medsci.uu.se
Melhus
Håkan
H
Karlsson
Julia
J
Kahan
Thomas
T
Malmqvist
Karin
K
Ohman
Peter
P
Nyström
Fredrik
F
Hägg
Anders
A
Lind
Lars
L
D000368:Aged; D000483:Alleles; D057911:Angiotensin Receptor Antagonists; D000808:Angiotensinogen / Q000235:genetics*; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001262:Atenolol / Q000627:therapeutic use*; D001713:Biphenyl Compounds / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D017379:Hypertrophy, Left Ventricular / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D000077405:Irbesartan; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin / Q000235:genetics*; D012084:Renin-Angiotensin System / Q000235:genetics; D013548:Sweden; D013777:Tetrazoles / Q000627:therapeutic use*
D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D001713:Biphenyl Compounds; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin; D013777:Tetrazoles; D000808:Angiotensinogen; D001262:Atenolol; D000077405:Irbesartan