Angiotensin II AT1 receptor gene polymorphism and microalbuminuria in essential hypertension

Abstract

The objective of this study was to analyze the relationship of polymorphisms of the angiotensin II AT1 receptor gene with microalbuminuria in a group of young adults with essential hypertension. Essential hypertensives, less than 50 years old, never previously treated with antihypertensive drugs, and in absence of diabetes mellitus were included. Office blood pressure (BP), 24-h ambulatory BP monitoring, urinary albumin excretion (UAE) measurements, and DNA analysis were performed. Polymorphisms of the angiotensin II AT1-receptor gene (A1166C and C573T) were studied by polymerase chain reaction and single-strand conformation polymorphism techniques. One hundred eighty-three patients, 49 (27%) microalbuminurics, were included. Office and ambulatory BP values were significantly higher in the microalbuminuria group. No differences in the presence of microalbuminuria were observed among the genotypes of either A1166C or C573T polymorphisms of the angiotensin II receptor AT1 gene, or in the allele frequency of the A1166C or the C573T polymorphism. LogUAE was significantly different among genotypes of the C573T polymorphism [CC 1.30(1.15-1.45), CT 1.14(1.00-1.28), and TT 0.94(0.68-1.20), P < .05]. Both office and ambulatory blood pressure and the TT/C573T genotype were independently related to logUAE, and, at the same BP values, UAE was lower in subjects with this genotype. We have found that the C573T polymorphism is on linkage disequilibrium with A1166C, as the 573T allele is closely linked to the presence of the 1166A allele, but not vice versa. Haplotype analysis among subjects with the AA genotype for the A1166C polymorphism confirms the influence of the TT genotype of the C573T polymorphism on the UAE in hypertensives. The C573T polymorphism of the angiotensin II receptor AT1 gene seems to be a genetic protective factor for UAE in a population of essential hypertensives.

Renin–angiotensin system gene polymorphisms: relationship with blood pressure and microalbuminuria in telmisartan-treated hypertensive patients

“…Amplification was conducted as described above. The A1166C and C573T polymorphisms of the AT1R gene were analyzed simultaneously by PCR using the technique of Chaves et al 9 PCR product was digested with 0.5 U FokI, and the resultant fragments were analyzed by the single-strand conformation polymorphism (SSCP) analysis using 10 Â 10 cm 2 10% acrylamide gel, 10% glycerol and 1 Â TEB buffer. The total digestion volume was mixed with 5 ml loading buffer (95% formamide, 20 mmol/l EDTA, 1% xylene cyanol and bromophenol blue).…”

“…The RAS plays a central role in the pathophysiology of vascular disease, 8 and the genes that regulate the system may contribute to the development of hypertension and end-organ damage. 9 The major active peptide of the RAS is angiotensin II. Produced from the precursor molecule, angiotensinogen (AGT), via an enzyme cascade involving ACE enzyme, angiotensin II exerts numerous effects on the homeostatic regulation of blood pressure, the vast majority of which are mediated via the angiotensin II type 1 receptor (AT1R).…”

“…Produced from the precursor molecule, angiotensinogen (AGT), via an enzyme cascade involving ACE enzyme, angiotensin II exerts numerous effects on the homeostatic regulation of blood pressure, the vast majority of which are mediated via the angiotensin II type 1 receptor (AT1R). 9 The presence of polymorphisms in the AGT, ACE and AT1R genes of the RAS has been associated with adverse cardiovascular changes. For example, the presence of the A-6G polymorphism of the AGT gene has been linked with increased body weight gain in hypertensive patients; 10 the insertion/deletion (I/D) polymorphisms of the ACE gene have been associated with increased blood pressure, urinary albumin excretion (UAE) and target-organ damage in hypertensive patients; 11 the A1166C polymorphism of the AT1R gene has been associated with hypertension, left ventricular hypertrophy, aortic stiffness and exaggerated vasoconstriction, whereas the C573T polymorphism in the same gene appears to confer protection against the development of microalbuminuria in patients with hypertension.…”

“…For example, the presence of the A-6G polymorphism of the AGT gene has been linked with increased body weight gain in hypertensive patients; 10 the insertion/deletion (I/D) polymorphisms of the ACE gene have been associated with increased blood pressure, urinary albumin excretion (UAE) and target-organ damage in hypertensive patients; 11 the A1166C polymorphism of the AT1R gene has been associated with hypertension, left ventricular hypertrophy, aortic stiffness and exaggerated vasoconstriction, whereas the C573T polymorphism in the same gene appears to confer protection against the development of microalbuminuria in patients with hypertension. 9 The role of genetic traits in predicting the response to antihypertensive drugs has been the subject of much research. Whether or not the response to treatment can be predicted from the presence of specific alleles of candidate genes has been the focus of several studies with heterogeneous results.…”

Polymorphisms of the angiotensinogen gene and the outcome of microalbuminuria in essential hypertension: a 3-year follow-up study

“…The genetic background, among other factors, could contribute to the development of microalbuminuria in hypertension. 7,8 The molecular variants of the angiotensinogen (AGT) gene, a key component of the renninangiotensin system (RAS), are considered genetic risk factors for primary hypertension. 9 Polymorphisms of the coding and the promoter regions, M235T and A-6G, respectively, have been linked to the AGT plasma levels and to the risk of hypertension in several studies, [10][11][12][13][14] but not in others.…”