Influence of the I/D polymorphism of the angiotensin-converting enzyme gene on the outcome of microalbuminuria in essential hypertension

The objective of the present study was to analyze the influence of the VD p olymorphism of the ACE gene on the outcome of microalbuminuria in essential hypertensive patients who were receiving antihypertensive treatment. One h undred thirty-six essential hypertensive patients who were <50 years old an d had never previously received treatment with antihypertensive drugs were included in the study. During a 3-year period, patients received nonpharmac ological treatment consisting of moderate salt restriction and a low-calori e diet they were obese, with or without a regimen of antihypertensive drugs based on beta-blockers or ACE inhibitors. Hydrochlorothiazide was added wh en necessary to maintain the blood pressure goal of <135/85 mm Hg. At the b eginning 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 i nsertion/deletion (I/D) polymorphism of the ACE gene was determined through the use of polymerase chain reaction. The variables used in the statistica l analysis were the measurements at the start of the study and the increase or decrease detected during the follow-up, estimated as individual specifi c regression line slope values. At baseline, no differences in blood pressu re or UAE values were observed among genotypes. Likewise, the genotype or a llele frequency was not significantly different between normoalbuminurics a nd microalbuminurics. After the 3 treatment years, significant reductions i n SEP, DBP, and UAE were found (SBP 151.6+/-17.3 reduced to 137.2+/-14.3 mm Hg, P<0.001; DBP 96.6+/-8.9 reduced to 84.5+/-9.8 mm Hg, P<0.001; UAE 36.7 +/-71.5 reduced to 28.3+/-78.6 mg/24 h, P<0.05). The slopes of these parame ters over rime did not differ significantly among genotypes. The slope of S EP was the main factor related to the slope of logUAE (P<0.003). A signific ant positive correlation coefficient between the SEP and logUAE slopes was observed for the DD patients (r=0.57, P<0.0001) but was absent in patients carrying the I allele (II r=-0.03, P=NS; I/D r=0.01, P=NS). Follow-up studi es should be used to achieve a better understanding of the impact of candid ate gene polymorphisms on the development of hypertension-induced organ dam age. Assessment of the VD polymorphism of the ACE gene may identify subject s who require a greatly lowered blood pressure to prevent organ damage and to reduce hypertension-associated complications and death.