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)

Abstract

SummaryBackground: 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 hyperten-

Endothelin-1 and hypertension: From bench to bedside

“…An A insertion into position 138 in the 5´UTR of the ET-1 gene has been associated with increased diastolic blood pressure [26]. The presence of the T allele in G5665T (198Lys/Asn) in exon 5 of the ET-1 gene was associated with elevated blood pressure, particularly in patients with a high body mass index [27][28][29] as well as an enhanced response to antihypertensive therapy in men [30]. Recently, the presence of the T allele in C1222T (1 kb downstream of the stop codon in the 3´UTR) in the ETRA gene was shown to correlate with decreased baroreflex sensitivity in normotensive and hypertensive individuals [31], whereas the presence of the AA allele in position 2013(+289)A/G in intron 17 of the ECE-1 gene was associated with increased basal blood pressure [32].…”

Pharmacokinetics and pharmacodynamics (PK/PD) of irbesartan in Beagle dogs after oral administration at two dose rates

“…Cythochrome P450 polymorphisms in different dog breeds could have potential implications for Irb pharmacokinetics in clinical studies and a wider variety in the general dog population might be expected. Additionally, the fact that the present findings are generated by a small sample size with only male subjects should also be taken into consideration as, in humans, gender differences (Hallberg et al 2004, Lam et al 2012) in drug metabolism (Borobia et al 2009) have been demonstrated.…”

Pharmacogenomics of Essential Hypertension: Are We Going the Right Way?

“…As it was found in the atenolol arm of the trial, the association between the preproendothelin-1 genotype and the BP reduction after therapy was gender-dependent [38].…”

“…In patients treated with atenolol, two AGT polymorphisms predicted the BP decline after therapy [36]. The same was true for the preproendothelin-1 genotype, but only in males [38]. With regard to the SILVHIA trial it must be emphasized that the results were based on a very small cohort, which limits its usefulness.…”

“…The SILVHIA (Swedish Irbesartan Left Ventricular Hypertrophy Investigation versus Atenolol) trial analysed the BP response to either a -blocker or an AT1R antagonist in relation to several genetic polymorphisms of the RAAS [35][36][37] and of the preproendothelin-1 [38]. These have been previously linked to essential hypertension or cardiovascular structure remodelling.…”