Influence of the I/D Polymorphism of the Angiotensin-Converting Enzyme Gene on the Outcome of Microalbuminuria in Essential Hypertension

Abstract

Abstract-The objective of the present study was to analyze the influence of the I/D polymorphism of the ACE gene on the outcome of microalbuminuria in essential hypertensive patients who were receiving antihypertensive treatment. One hundred thirty-six essential hypertensive patients who were Ͻ50 years old and had never previously received treatment with antihypertensive drugs were included in the study. During a 3-year period, patients received nonpharmacological treatment consisting of moderate salt restriction and a low-calorie diet they were obese, with or without a regimen of antihypertensive drugs based on ␤-blockers or ACE inhibitors. Hydrochlorothiazide was added when necessary to maintain the blood pressure goal of Ͻ135/85 mm Hg. At the beginning of the study and at yearly intervals, systolic and diastolic blood pressures (SBP and DBP, respectively), 24-hour urinary albumin excretion (UAE), renal function, and biochemical profile measurements were made. The insertion/deletion (I/D) polymorphism of the ACE gene was determined through the use of polymerase chain reaction. The variables used in the statistical analysis were the measurements at the start of the study and the increase or decrease detected during the follow-up, estimated as individual specific regression line slope values. At baseline, no differences in blood pressure or UAE values were observed among genotypes. Likewise, the genotype or allele frequency was not significantly different between normoalbuminurics and microalbuminurics. After the 3 treatment years, significant reductions in SBP, DBP, and UAE were found (SBP 151.6Ϯ17.3 reduced to 137.2Ϯ14.3 mm Hg, PϽ0.001; DBP 96.6Ϯ8.9 reduced to 84.5Ϯ9.8 mm Hg, PϽ0.001; UAE 36.7Ϯ71.5 reduced to 28.3Ϯ78.6 mg/24 h, PϽ0.05). The slopes of these parameters over time did not differ significantly among genotypes. The slope of SBP was the main factor related to the slope of logUAE (PϽ0.003). A significant positive correlation coefficient between the SBP and logUAE slopes was observed for the DD patients (rϭ0.57, PϽ0.0001) but was absent in patients carrying the I allele (II rϭϪ0.03, PϭNS; I/D rϭ0.01, PϭNS). Follow-up studies should be used to achieve a better understanding of the impact of candidate gene polymorphisms on the development of hypertension-induced organ damage. Assessment of the I/D polymorphism of the ACE gene may identify subjects who require a greatly lowered blood pressure to prevent organ damage and to reduce hypertensionassociated complications and death.

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

“…[22][23] The most common analytical approach is to look for associations in cross-sectional studies, and less commonly to analyse the outcomes of prospective studies. 7 Studies analysing data at large offer a more powerful tool than the crosssectional studies do. In the present study, we have studied the influence of the AGT polymorphism in the UAE of essential hypertensives by observing its impact on the outcome of microalbuminuria during antihypertensive treatment.…”

“…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.…”

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

“…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. 9 The role of genetic traits in predicting the response to antihypertensive drugs has been the subject of much research.…”

Long-Term Impact of Systolic Blood Pressure and Glycemia on the Development of Microalbuminuria in Essential Hypertension

“…Microalbuminuria has been related to blood pressure (BP) values 14 -17 and to hyperinsulinemia as an expression of insulin resistance. 18,19 Obesity, 20 smoking, 21 and genetics 22,23 have also been implicated as determinants of microalbuminuria in some of the studies.Follow-up studies of microalbuminuria in essential hypertensives are rare, 4,24 -26 and information about the contribution of factors other than BP reduction on the changes of UAE over time is lacking. Thus, the objective of the present study was to assess the long-term impact of factors related to the development of microalbuminuria during follow-up for a group of young adult normoalbuminurics with essential hypertension who had never received antihypertensive treatment.…”

“…Microalbuminuria has been related to blood pressure (BP) values 14 -17 and to hyperinsulinemia as an expression of insulin resistance. 18,19 Obesity, 20 smoking, 21 and genetics 22,23 have also been implicated as determinants of microalbuminuria in some of the studies.…”