Impact of ACE I/D gene polymorphism on congenital renal malformations.
To investigate the role of the angiotensin converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism on prevalence and progression of disease in children with chronic renal failure (CRF), we determined the ACE I/D genotype in 95 children with CRF due to renal malformations (hypo-/dysplasia, obstructive uropathy, reflux nephropathy; n = 59), other congenital or hereditary diseases (n = 23), or acquired glomerular disorders (n = 13), who had been followed prospectively over a 2-year period. CRF progression rate was followed in each individual by linear regression analysis of estimates of glomerular filtration rate (GFR) obtained every 2 months. Actuarial renal 'survival' analysis was performed, using a GFR loss of 10 ml/min per 1.73 m2 as a cutoff point. The distribution of the ACE genotype did not differ among the disease groups. There was also no difference in ACE genotype distribution between the patients and a control group of healthy Caucasian children (n = 163). Among the children with renal malformations, the 2-year renal survival was significantly lower in those with the DD genotype (61%) than in patients with ID or II genotype (89%, P < 0.01). In the other disease groups, the ACE I/D genotype was not predictive of CRF progression. In a multivariate analysis of risk factors, the adverse effect of the DD genotype (risk ratio 10.2, P < 0.05) was independent of and additive to those of arterial hypertension (RR 13.2, P < 0.001) and gross proteinuria (RR 4.7, P < 0.05). We conclude that the ACE DD genotype is a significant risk factor for children with congenital renal malformations to develop progressive CRF. The effect of the ACE polymorphism in this patient group is independent of hypertension and proteinuria.
Hohenfellner
K
K
University Children's Hospital, Langenbeckstrasse 1, 55101 Mainz, Germany. hohenfellner@web.de
Wingen
A M
AM
Nauroth
O
O
Wühl
E
E
Mehls
O
O
Schaefer
F
F
D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D004251:DNA Transposable Elements; D018450:Disease Progression; D017353:Gene Deletion; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007668:Kidney / Q000002:abnormalities*; D007676:Kidney Failure, Chronic / Q000209:etiology / Q000235:genetics; D015999:Multivariate Analysis; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D011446:Prospective Studies; D016019:Survival Analysis
D004251:DNA Transposable Elements; D007703:Peptidyl-Dipeptidase A