Association between polymorphisms of genes involved in the Renin-Angiotensin-Aldosterone System and the adaptive morphological and functional responses to essential hypertension.

Hypertensive cardiac remodeling is illustrated by increased left ventricular (LV) mass index values and/or relative wall thickness (RWT) values >0.42, and functionally by isolated alteration of LV diastole (abnormal relaxation). The aim of the present study was to establish differentiated models of anatomical and functional adaptation to essential hypertension (EHT), in relation to the genetic variants of genes involved in the Renin-Angiotensin-Aldosterone System (RAAS). The -AGT, -ACE, -R1AngII, -R2AngII and -REN genotypes were determined using PCR-Restriction Fragment Length Polymorphism in 139 hypertensive subjects. The relationship between the studied RAAS gene polymorphisms with morphological and functional cardiac remodeling was assessed by multiple logistic regression analysis. Patients carrying the , genotypes (-R2AngII polymorphism) had a 2.72-fold (P=0.033) increased risk of exhibiting an RWT value <0.42; in the multivariate model the risk was 4.02-fold higher (P=0.008). Analysis of LV diastolic dysfunction (LVDD) revealed that hypertensive patients carrying the , genotypes (-AGT polymorphism) had a 2.24-fold (P=0.037) increased risk of developing LVDD and a 2.42-fold increased risk (P=0.039) after adjustment for confounders. Similarly, carriers of the , genotypes (-REN) had a 2.32-fold (P=0.021) increased risk of developing LVDD, and this remained an independent risk factor based on the multivariate model (P=0.033). The results of the present study showed that no particular gene was associated with increased LV mass, but the -R2AngII polymorphism was associated with a non-concentric type of cardiac response in hypertensive patients. Conversely, the -AGT and -REN polymorphisms were found to be statistically significantly associated with LVDD when assessing abnormal relaxation.