Renin-angiotensin-aldosterone system gene variants and their association with left ventricular function and vascular properties in essential hypertension

Abstract

Purpose: The role of the renin-angiotensin-aldosterone system in the pathophysiology of organ damage still remains elusive. The angiotensinogen M235T and aldosterone synthase C-344T gene polymorphisms may be associated with vascular indices, renal function and left ventricular hypertrophy. Therefore, in the present study we sought to investigate their potential associations with left ventricular function and vascular properties in essential hypertension. Methods: The study population consisted of 319 untreated patients, newly diagnosed stage I–II essential hypertension and a control group, consisted of 191 age-matched for classical cardiovascular risk factors. The gene mutations frequencies was determined using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. In all participants, flow mediated dilation (FMD), pulse wave velocity (PWV), intima-media thickness (IMT), as well as the incidence and progression of retinopathy were evaluated. Left cardiac indices were assessed by echocardiography. Glomerular filtration rate (GFR) was estimated by Cockcroft-Gault formula. Results: 235TT homozygotes compared with M-carriers had significantly lower FMD in controls (p=0.038) and higher PWV values in hypertensive patients (p=0.025). Regarding other vascular properties no other significant associations were observed. TT homozygosity showed a trend towards lower GFR compared with MM+MT genotype in hypertensive patients (99.9±30.2 vs 106.8±35.3 mL/min/1.73 m2, p=0.067) but neither genotype was associated with increased creatinine. Notably, we observed higher values of IMT in -344TT homozygosity, in the group of hypertensives (781.6±33.5 vs 712.5±16.2 μm, p=0.039). Moreover, -344TT hypertensives exhibited higher values of left ventricular mass index compared to C-allele carriers (p=0.020) and higher prevalence of concentric hypertrophy (p<0.001). Conclusions: The present study suggests that aldosterone synthase is associated with left ventricular hypertrophy, while angiotensinogen is associated with endothelial dysfunction, increased IMT and arterial stiffness in untreated hypertension. These findings suggest that both variants play important role in the pathophysiology of hypertension.