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)
2004 (English)In: Clinical Cardiology, ISSN 0160-9289, Vol. 27, no 3, 169-73 p.Article in journal (Refereed) Published
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. HYPOTHESIS: 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.
Place, publisher, year, edition, pages
2004. Vol. 27, no 3, 169-73 p.
Antihypertensive Agents/*therapeutic use, Atenolol/therapeutic use, Biphenyl Compounds/*therapeutic use, Double-Blind Method, Female, Genotype, Humans, Hypertension/complications/*drug therapy, Hypertrophy; Left Ventricular/complications/*drug therapy/physiopathology, Linear Models, Male, Polymorphism; Genetic, Research Support; Non-U.S. Gov't, Sweden, Tetrazoles/*therapeutic use, Transforming
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-65946DOI: 10.1002/clc.4960270315PubMedID: 15049387OAI: oai:DiVA.org:uu-65946DiVA: diva2:93857