Impact of ACE I/D gene polymorphism on congenital renal malformations |
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Authors: | K Hohenfellner Anne-Margret Wingen Oliver Nauroth Elke Wühl Otto Mehls Franz Schaefer |
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Affiliation: | (1) University Children’s Hospital, Langenbeckstrasse 1, 55101 Mainz, Germany e-mail: hohenfellner@web.de Tel.: +49-6131-173560, Fax: +49-6131-173918, DE;(2) Department of Pediatric Nephrology, University Children’s Hospital, Essen, Germany, DE;(3) Department of Pediatric Nephrology, University Children’s Hospital, Heidelberg, Germany, DE |
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Abstract: | 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.
Received: 25 August 2000 / Revised: 10 December 2000 / Accepted: 15 December 2000 |
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Keywords: | ACE gene polymorphism Congenital renal malformation Progression of chronic renal failure |
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