The deletion polymorphism of the angiotensin-converting enzyme is associated with nephroangiosclerosis

Abstract

The D allele of the angiotensin-converting enzyme (ACE) gene has been linked with diabetic nephropathy and IgA glomerulonephritis and with faster renal disease progression. The association of this allele with nephroangiosclerosis has been scarcely investigated. We have tested this association in 45 hypertensive patients (all whites) with well defined nephroangiosclerosis (diagnosis established on the basis of renal biopsy in all cases) and moderate to severe renal failure. As studies of genetic association of small size often produce conflicting results, besides a control group of 343 Italian patients with essential hypertension and normal renal function, we elected to use also a very large control group of race-matched subjects taken from a meta-analysis of 27,565 whites. The proportion of patients with the D allele (64%) was higher in patients with nephroangiosclerosis than that in Italian hypertensives (54%) and in whites (54%). DD and DI genotypes were more prevalent in patients than in control groups. The dominant model (DD and DI v II: nephroangiosclerosis v Italian controls: chi2 = 6.19, P = .012; nephroangiosclerosis v whites chi2 = 6.86, P = .009) fitted the data better than the codominant and the recessive model (P < or = .022). The D allele is associated with nephroangiosclerosis with a dominant effect in the sample of patients studied. Although intervention studies are needed to see whether these findings imply a causal association, our data suggest that this allele may at least act as disease marker in nephroangiosclerosis.

Genetic bases of urinary albumin excretion and related traits in hypertension

“…One retrospective study found a significantly higher prevalence of the DD genotypes in patients with nephroangioesclerosis diagnosed by biopsy compared with hypertensive patients without renal damage [22], a finding replicated in an independent Italian cohort of hypertensive patients with or without renal damage [47].…”

Angiotensin-Converting Enzyme Gene Polymorphism and N-Acetyl-β-<i>D</i>-Glucosaminidase Excretion in Endemic Nephropathy

“…Just as in diabetes [28,36,47,48] or IgA nephropathy [29,30], it could not be concluded that ACE I/D polymorphism is a genetic marker in EN. However, as it was observed in other CKD types [31,32,33,34,49], it might modulate the clinical course and determine the decline in renal function.…”

“…The RAS and polymorphism of its components are well known for their significant role in the progression of renal disease [23,24,25,26,27,28,29,30,31,32,33,34]. Over the past decades, particular attention has been paid to the angiotensin-converting enzyme (ACE) gene polymorphism, and some authors have reported that the outcome of renal disease in homozygotes with deletion (D) of 287 bp in intron 16 of the ACE gene was poorer than in other patients [23,24,25,35,36].…”

Multifactorial Determination of Hypertensive Nephroangiosclerosis

“…A few genes of this system have been examined [161][162][163], but only angiotensin-1-converting enzyme (ACE) insertion/deletion polymorphism is believed to be clearly associated with an increased risk of renal complications of essential hypertension. In a study of 45 patients with biopsy-proven HN and two control groups with a total of 27,908 individuals, the proportion of subjects with the D allele (64%) was higher in the sample of studied patients than that in the control (54%) [164]. DD and DI genotypes were also more prevalent in the group with HN than in the control groups.…”