Transforming growth factor beta1 genotype and change in left ventricular mass during antihypertensive treatment--results from the Swedish Irbesartan Left Ventricular Hypertrophy Investigation versus Atenolol (SILVHIA).
BACKGROUND
Angiotensin II, via the angiotensin II type 1 (AT1) receptor, may mediate myocardial fibrosis and myocyte hypertrophy seen in hypertensive left ventricular (LV) hypertrophy through production of transforming growth factor beta1 (TGF-beta1); AT1-receptor antagonists reverse these changes. The TGF-beta1 G + 915C polymorphism is associated with interindividual variation in TGF-beta1 production. No study has yet determined the impact of this polymorphism on the response to antihypertensive treatment.


OBJECTIVE
We aimed to determine whether the TGF-beta1 G + 915C polymorphism was related to change in LV mass during antihypertensive treatment with either an AT1-receptor antagonists or a beta1-adrenoceptor blocker. The polymorphism was hypothesized to have an impact mainly on the irbesartan group.


METHODS
We determined the association between the TGF-beta1 genotype and regression of LV mass in 90 patients with essential hypertension and echocardiographically diagnosed LV hypertrophy, randomized in a double-blind study to receive treatment for 48 weeks with either the AT1-receptor antagonist irbesartan or the beta1-adrenoceptor blocker atenolol.


RESULTS
Irbesartan-treated patients who were carriers of the C-allele, which is associated with low expression of TGF-beta1, responded with a markedly greater decrease in LV mass index (LVMI) than subjects with the G/G genotype (adjusted mean change in LVMI -44.7 g/m2 vs. -22.2 g/m2, p = 0.007), independent of blood pressure reduction. No association between genotype and change in LVMI was observed in the atenolol group.


CONCLUSIONS
The TGF-beta1 G + 915C polymorphism is related to the change in LVMI in response to antihypertensive treatment with the AT1-receptor antagonist irbesartan.
Hallberg
Pär
P
Department of Medical Sciences, Uppsala University, Uppsala, Sweden. par.hallberg@medsci.uu.se
Lind
Lars
L
Billberger
Katarina
K
Michaelsson
Karl
K
Karlsson
Julia
J
Kurland
Lisa
L
Kahan
Thomas
T
Malmqvist
Karin
K
Ohman
K Peter
KP
Nyström
Fredrik
F
Liljedahl
Ulrika
U
Syvänen
Ann-Christine
AC
Melhus
Håkan
H
D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001262:Atenolol / Q000627:therapeutic use; D001713:Biphenyl Compounds / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000188:drug therapy*; D017379:Hypertrophy, Left Ventricular / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D000077405:Irbesartan; D016014:Linear Models; D008297:Male; D011110:Polymorphism, Genetic; D013548:Sweden; D013777:Tetrazoles / Q000627:therapeutic use*; D016212:Transforming Growth Factor beta / Q000235:genetics*; D016896:Treatment Outcome
D000959:Antihypertensive Agents; D001713:Biphenyl Compounds; D013777:Tetrazoles; D016212:Transforming Growth Factor beta; D001262:Atenolol; D000077405:Irbesartan