The relation between ACE D/I and CYP11B2 C-344T polymorphisms and parameters of arterial stiffness in the context of renal sodium handling

Abstract

Background. Sodium overload is related to the development of primary hypertension and its complications. Methods. In 131 (65 female) treated hypertensives (average blood pressure 144/82 mmHg and duration of hypertension 11.7 years), we measured peripheral and central arterial pressures, peripheral (AIxP) and central (AIxC1, AIxC2) augmentation indices, pulse-wave velocity (PWV) and daily urinary sodium excretion, and conducted genetic studies of ACE D/I and CYP11B2 C-344T polymorphisms. Proximal (FELi) and distal (FDRNa) sodium reabsorption measurements were performed using endogenous lithium clearance. Results. We found statistically significant interactions between FELi and ACE D/I polymorphism with respect to AIxC2 (PINT = 0.05) and between FELi and CYP11B2 C-344T polymorphism with respect to AIxC1 (PINT = 0.01), AIxC2 (PINT = 0.04) and AIxP (PINT = 0.01). In the group of ACE I allele carriers compared with DD homozygotes, the AIxC1 (154.1 vs 140.6%; p = 0.02), AIxC2 (33.3 vs 26.9%; p = 0.02) and AIxP (94.6 vs 85.2%; p = 0.01) were higher in the subgroup with FELi below the median value (FELi1), but not in the subgroup with FELi above the median value (FELi2). In the group of CYP11B2 TT homozygotes compared with C allele carriers, we observed higher values of AIxC1 (158.5 vs 146.4%; p = 0.03), AIxC2 (36.0 vs 29.4%; p = 0.01) and AIxP (99.0 vs 88.7%; p = 0.005) in the FELi1 but not the FELi2 subgroup. Conclusions. In the population with assumed high dietary sodium intake and long-standing history of hypertension, the relation between proximal sodium reabsorption and the development of arterial stiffness depends on the genetic context of the selected genetic polymorphisms of the renin—angiotensin—aldosterone system, independent of blood pressure.