Gender-specific association between preproendothelin-1 genotype and reduction of systolic blood pressure during antihypertensive treatment -: Results from the Swedish Irbesartan Left Ventricular Hypertrophy Investigation versus Atenolol (SILVHIA)

Background: Studies suggest that endothelin-1 contributes to the pathogenesis of hypertension. A G5665T gene polymorphism of preproendothelin-1 has been shown to be associated with higher blood pressure in overweight patients. No study has yet determined the effect of this polymorphism on the change in blood pressure during antihypertensive treatment. Hypothesis: This study aimed to determine this effect in hypertensive patients with left ventricular (LV) hypertrophy during antihypertensive treatment with either irbesartan or atenolol. Methods: We determined the preproendothelin-1 genotype using minisequencing in 102 patients with essential hypertension and LV hypertrophy verified by echocardiography, randomized in a double-blind fashion to treatment with either the AT(1)-receptor antagonist irbesartan or the beta(1)-adrenoceptor antagonist atenolol. Results: The change in systolic blood pressure (SBP) after 12 weeks of treatment was related to the preproendothelin-1 genotype in men; after adjustment for potential covariates (age, blood pressure, and LV mass index at study entry, dose of irbesartan/atenolol, and type of treatment), those carrying the T-allele responded on average with a more than two-fold greater reduction than those with the G/G genotype (-21.9 mmHg [3.9] vs. -8.9 [2.3], p = 0.007). No significant differences in blood pressure change between G/G and carriers of the T-allele were seen among women. Conclusions: Our finding suggests a gender-specific relationship between the G5665T preproendothelin-1 polymorphism and change in SBP in response to antihypertensive treatment with irbesartan or atenolol, suggesting the endothelin pathway to be a common mechanism included in the hypertensive action of the drugs.