THE DELETION POLYMORPHISM OF THE ANGIOTENSIN I-CONVERTING ENZYME GENEIS ASSOCIATED WITH TARGET ORGAN DAMAGE IN ESSENTIAL-HYPERTENSION

The activity of the renin-angiotensin-aldosterone system is thought to play a significant role in the development of target organ damage in essential hypertension. An insertion/deletion (I/D) polymorphism of th e angiotensin I-converting enzyme (ACE) gene has recently been associa ted with increased risk for left ventricular hypertrophy and coronary heart disease in the general population. The D allele is associated wi th higher levels of circulating ACE and therefore may predispose to ca rdiovascular damage. The study presented here was performed to investi gate the association between the ACE genotype, microalbuminuria, retin opathy, and left ventricular hypertrophy in 106 patients with essentia l hypertension. ACE gene polymorphism was determined by polymerase cha in reaction technique. Microalbuminuria was evaluated as albumin-to-cr eatinine ratio (A/C) in three nonconsecutive first morning urine sampl es (negative urine culture) after a 4-wk washout period. Microalbuminu ria was defined as A/C between 2.38 to 19 (men) and 2.96 to 20 (women) . Hypertensive retinopathy was evaluated by direct funduscopic examina tion (Keith-Wagener-Barker classification) and left ventricular hypert rophy by M-B mode echodardiography. The distribution of the DD, ID, an d II genotypes was 27, 50, and 23%, respectively. The prevalence of mi croalbuminuria, retinopathy, and left ventricular hypertrophy was 19, 74, and 72% respectively. There were no differences among the three ge notypes for age, known duration of disease, body mass index, blood pre ssure, serum glucose, uric acid, and lipid profile. DD and ID genotype s were significantly associated with the presence of microalbuminuria (odds ratio, 8.51; 95% confidence interval, 1.07 to 67.85; P = 0.019), retinopathy (odds ratio, 5.19; 95% confidence interval, 1.71 to 15.75 ; P = 0.005) and left ventricular hypertrophy (odds ratio, 5.22; 95% c onfidence interval, 1.52 to 17.94; P = 0.016), Furthermore, patients w ith DD and ID genotypes showed higher levels of A/C (3.6 +/- 0.9, DD; 2.6 +/- 0.7, ID; 0.9 +/- 0.2 mg/mmol, II; P = 0.0015 by analysis of va riance) and increased left ventricular mass index (152 +/- 4.7, DD+ID versus 133 +/- 5.7 g/m(2), II; P = 0.01) compared with II patients. Th e D allele was significantly more frequent in patients with microalbum inuria (odds ratio, 2.59; 95% confidence interval, 1.24 to 5.41; P = 0 .013) and in those with retinopathy (odds ratio, 2.44; 95% confidence interval, 1.21 to 4.90; P = 0.015). Multiple regression analyses perfo rmed among the entire cohort of patients demonstrated that ACE genotyp e significantly and independently influences the presence of retinopat hy, left ventricular hypertrophy, and microalbuminuria, In conclusion, the D allele of the ACE gene is associated with microalbuminuria as w ell as with retinopathy and left ventricular hypertrophy, and seems to be an independent risk factor for target organ damage in essential hy pertension.