Transforming growth factor β1 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 type1 (AT(1)) receptor, may mediate myocardial fibrosis and myocyte hypertrophy seen in hypertensive left ventricular (LV) hypertrophy through production of transforming growth factor beta(1) (TGF-beta(1)); AT(1)-receptor antagonists reverse these changes. The TGF-beta(1) G + 915C polymorphism is associated with interindividual variation in TGF-beta(1) production. No study has yet determined the impact of this polymorphism on the response to antibypertensive treatment. Hypothesis: We aimed to determine whether the TGF-beta(1) G + 915C polymorphism was related to change in LV mass during antilrypertensive treatment with either an AT(1) -receptor antagonists or a beta(1)-adrenoceptor blocker. The polymorphism was hypothesized to have an impact mainly on the irbesartan group. Methods: We determined the association between the TGFbeta(1) 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 AT(1) -receptor antagonist irbesartan or the beta(1)-adrenoceptor blocker atenolol. Results: Irbesartan-treated patients who were carriers of the C-allele, which is associated with low expression of TGF-beta(1), 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/m(2) vs. -22.2 g/m(2), 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-beta(1) G + 915C polymorphism is related to the change in LVMI in response to antihypertensive treatment with the AT(1)-receptor antagonist irbesartan.