Angiotensin converting enzyme gene I/D polymorphism in essential hypertension and nephroangiosclerosis

Abstract

An insertion/deletion (I/D) polymorphism of the angiotensin converting enzyme (ACE) gene significantly influences circulating ACE levels and plays a role in the development of target organ damage, that is, left ventricular hypertrophy in essential hypertension (EH), and microalbuminuria in diabetes mellitus. We have examined the role of the I/D polymorphism in essential hypertensive patients with renal involvement. The study was divided in two independent protocols. In protocol 1, we retrospectively analyzed the ACE genotypes in 37 essential hypertensive patients with a clinical and histopathological diagnosis of nephroangiosclerosis. In protocol 2, ACE genotypes as well as microalbuminuria and renal hemodynamic parameters were investigated in 75 patients with EH with normal renal function and a strong family history of hypertension. As control group, 75 healthy subjects with BP < 130/85 mm Hg and no family history of cardiovascular diseases were studied. The ACE variants were determined by PCR and the genotypes were classified as DD, DI and II. In protocol 1, patients with nephroangiosclerosis displayed a significant difference in the genotype distribution (57% DD, 27% DI, 16% II) when compared to the control population (25% DD, 64% DI, 11% II; P < 0.001). There was no significant difference in genotype distribution between hypertensive patients with normal renal function (protocol 2; 33% DD, 59% DI, 8% II) and the control group. There were no differences in age, blood pressure, microalbuminuria and duration of the disease among the three genotypes in the EH group from protocol 2. Taken together, these findings suggest that the DD genotype of ACE is associated with histopathologic-proven kidney involvement in patients with EH and that this polymorphism could be a potential genetic marker in hypertensives at risk of renal complications.

Genetics of arterial hypertension and hypotension

“…Another recent review counted 12 positive and 14 'negative' publications on this issue (Agarwal et al 2005). Likewise, available evidence suggest that the D allele causes a modest-and most likely irrelevant-increase in the risk for other cardiovascular and renal diseases (Cambien et al 1992;Schunkert et al 1994;Iwai et al 1994;Pontremoli et al 1996;Fernandez-Llama et al 1998). For these entities, meta-analyses revealed odds ratios for carriers of the DD genotype ranging from 1.04-1.43 for myocardial infarction (Agerholm-Larsen et al 2000;Keavney et al 2000) and from 1.28-1.56 (Staessen et al 1997;Ng et al 2005) for diabetic nephropathy.…”

Lack of association between ACE gene polymorphism and left ventricular hypertrophy in essential hypertension

“…13 Subjects were classified as II, DD or heterozygote for insertion/deletion (DI). Mistyping of DI heterozygotes as DD due to preferential amplification of the D allele and inefficiency in amplification of the I allele has been described.…”

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

“…15,16 Crosssectional association studies, meanwhile, have reported a lack of impact of the polymorphisms of the AGT gene on microalbuminuria. [17][18][19] Observing the changes in microalbuminuria during antihypertensive treatment in patients carrying different alleles of the polymorphisms is another potential approach to studying whether or not polymorphisms of the AGT gene influence microalbuminuria. In the present study, the influence of the A-6G polymorphisms of the AGT gene on the outcome of microalbuminuria during a 3-year antihypertensive treatment was analysed in a group of young adults with essential hypertension, never previously treated with antihypertensive drugs.…”