Angiotensinogen gene polymorphisms: relationship to blood pressure response to antihypertensive treatment. Results from the Swedish Irbesartan Left Ventricular Hypertrophy Investigation vs Atenolol (SILVHIA) trial.
BACKGROUND
The renin-angiotensin-aldosterone system (RAAS) is important for the development of hypertension, and several antihypertensive drugs target this system. Our aim was to determine whether specific single nucleotide polymorphisms (SNPs) in RAAS genes were related to the blood pressure (BP) lowering effect of antihypertensive treatment.


METHODS
Patients with mild to moderate primary hypertension and left ventricular hypertrophy were randomized in a double-blind fashion to treatment with either the angiotensin II type 1 receptor antagonist irbesartan (n = 48) or the beta(1)-adrenergic receptor blocker atenolol (n = 49) as monotherapy. A microarray-based minisequencing system was used to genotype 30 SNPs in seven genes in the RAAS. These polymorphisms were related to the antihypertensive response after 12 weeks treatment.


RESULTS
The BP reductions were similar in the atenolol and the irbesartan groups. Presence of the angiotensinogen (AGT) -6A allele or the AGT 235T allele were both associated with the most pronounced systolic BP response to atenolol treatment (P =.001 when -6 AA+AG was compared with GG and P =.008 for presence of the 235T variant compared with 235 MM).


CONCLUSIONS
We found that SNPs in the angiotensinogen gene were associated with the BP lowering response to atenolol. This study is limited by a relatively small sample size, and the results should therefore be viewed as preliminary. Despite this limitation, these results illustrate the potential of using SNP genotyping as a pharmacogenetic tool in antihypertensive treatment.
Kurland
Lisa
L
Department of Medical Sciences, Uppsala University Hospital, Uppsala, Sweden. lisa.kurland@medsci.uu.se
Liljedahl
Ulrika
U
Karlsson
Julia
J
Kahan
Thomas
T
Malmqvist
Karin
K
Melhus
Håkan
H
Syvänen
Ann Christine
AC
Lind
Lars
L
D047228:Angiotensin II Type 1 Receptor Blockers; D000808:Angiotensinogen / Q000235:genetics*; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001262:Atenolol / Q000627:therapeutic use*; D001713:Biphenyl Compounds / Q000627:therapeutic use*; D001794:Blood Pressure; D004311:Double-Blind Method; D005260:Female; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000188:drug therapy / Q000235:genetics*; D017379:Hypertrophy, Left Ventricular / Q000209:etiology; D000077405:Irbesartan; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012084:Renin-Angiotensin System / Q000235:genetics*; D013777:Tetrazoles / Q000627:therapeutic use*; D016896:Treatment Outcome
D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D001713:Biphenyl Compounds; D013777:Tetrazoles; D000808:Angiotensinogen; D001262:Atenolol; D000077405:Irbesartan