Renin-angiotensin-aldosterone system genotypes and cardiac remodeling response to essential hypertension

Abstract

Abstract Background/Introduction Cardiac remodeling represent a response to uncontrolled essential hypertension (EHT). The morphological response is expressed by left ventricular (LV) mass index values and/or relative wall thickness (RWT) >0.42. Functionally response is expressed by isolated alteration of LV diastolic function (E/A<1). Purpose We aimed to establish the association between anatomical and functional adaptation to EHT, with two genetic variants of the renin-angiotensin-aldosterone system (RAAS): M235T-AGT and A3123C-R2 AngII. Methods In 139 hypertensive subjects cohort, we determined the M235T-AGT and A3123C-R2 AngII genotypes, using polymerase chain reaction-restriction fragment length polymorphism methods. The relationship between the studied RAAS gene polymorphisms and morphological and functional cardiac remodeling was assessed by multiple logistic regressions. Results We found that the C/C, A/C genotypes of the A3123C-R2 AngII polymorphism were statistically significantly associated with RWT<0.42 (p=0.033), so hypertensive patients carrying this genotype had a 2.7-fold increased risk to have a non-concentric type of cardiac response. The association was maintained even after adjustment for confounders - age, body mass index (BMI), systolic blood pressure (BP), and diastolic BP (p=0.008). We found statistically significant associations between LV diastolic dysfunction in hypertensive patients cohort carrying the T/T, M/T genotypes (M235T-AGT polymorphism) (p=0.037). Moreover, the association remained statistically significant even after adjustment for age, BMI, systolic BP, and diastolic BP (p=0.039). We could not identify any statistically significant associations between M235T-AGT, A3123C-R2 AngII polymorphisms, and LV mass index. Conclusion(s) Non-concentric type of cardiac response to essential hypertension was associated with A3123C-R2 AngII polymorphism. M235T-AGT polymorphism was found to be statistically significantly associated with alteration of LV diastolic function. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): “Iuliu Hatieganu” University of Medicine and Pharmacy Cluj-Napoca, as part of Doctoral Research Projects (DRP) 2016