Genetic polymorphisms of the renin-angiotensin-aldosterone system and renal insufficiency in essential hypertension

Abstract

Objective The renin–angiotensin–aldosterone system (RAAS) plays an important role in the control of renal function both in physiological and pathological conditions. The aim of the present study was to evaluate the relation between four genetic polymorphisms of the RAAS and renal insufficiency in a population of patients with essential hypertension living in north-east Italy. Design and methods Eighty-six hypertensive patients with renal insufficiency and 172 hypertensive patients without renal damage matched for age and hypertension duration to within 2 years were evaluated. Genotyping for insertion/ deletion of angiotensin-converting enzyme (ACE I/D), angiotensinogen (AGT) M235T, angiotensin II type 1 receptor (AT1R) A1166C and aldosterone synthase (CYP11B2) –344C/T polymorphisms were performed using polymerase chain reaction, with further restriction analysis when required. Results Each of the genetic polymorphisms of the RAAS genes was associated with renal failure; the adjusted odds ratios were 1.47 and 1.89 for ACE D allele, assuming a co dominant and a recessive mode of inheritance, respectively; 1.51 for AGT T235 allele assuming a co dominant, and 1.98 assuming a recessive, pattern of inheritance; 1.79 for AT1R C1166 allele considering a dominant pattern; and 3.89 for CYP11B2 S344C allele as a recessive effect. However, CYP11B2 genotypes were not in Hardy–Weinberg equilibrium among controls. The associations AGT TT– AT1R AC and CYP11B2 CC–ACE DD showed a possible positive interaction in the development of renal insufficiency among hypertensive subjects. The association AGT MM– AT1R AA and AGT MM–AT1R AA–CYP11B2 TT or TC combinations were associated with a reduced risk for renal failure. Conclusions Our findings suggest that in patients with essential hypertension an unfavorable genetic pattern of RAAS may contribute to the increased risk for the development of renal failure