Genetic Polymorphism of the Renin-Angiotensin System on the Development of Primary Vesicoureteral Reflux

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Background: The familial clustering of vesicoureteral reflux (VUR) has suggested a genetic basis. This study was designed to investigate the genetic polymorphism of the renin-angiotensin system (RAS) in Korean children. Methods: Genetic polymorphism of angiotensin-converting enzyme (ACE) and angiotensin II receptor genes was evaluated in 67 primary VUR patients and compared to 58 controls with no urological abnormalities. To detect the relation of the risk factors of primary VUR with the genetic polymorphism, the distribution of ACE, AT1 and AT2 genotypes after stratification by risk factors was also studied in the primary VUR patients. Results: The incidence of AT2 A-1332G transition was significantly lower in primary VUR patients (p = 0.047). Furthermore, in the case of combination of ACE and AT2 gene, a significantly lower incidence of primary VUR was seen with II genotype of ACE and A-1332G transition in the AT2 receptor gene (p = 0.003). Concerning the risk factors of primary VUR, there were no biologically significant results. Conclusions: These findings indicate that a lower incidence of AT2 A-1332G transition is seen in primary VUR patients, at least in the Korean population. Also, in the case of combination of ACE and AT2 gene, the combination of ACE II genotype and AT2 A-1332G transition occurs infrequently in primary VUR.

Related collections

Most cited references 12

Record: found
Abstract: found
Article: not found

Genetic polymorphisms of the renin-angiotensin system and the outcome of focal segmental glomerulosclerosis in children.

N Ish-Shalom, C. A. Drukker, D Halle … (1998)

The clinical course of primary focal segmental glomerulosclerosis (FSGS) in children is variable, with some patients having a much more rapidly progressing course than others. The purpose of our study was to compare the frequency of three polymorphisms of the renin-angiotensin system (RAS) in children with FSGS with that in healthy controls of matching ethnic groups, and to determine whether the clinical outcome of FSGS was associated with different RAS genotypes. Three RAS genotypes were examined in 47 Jewish and Arab children with biopsy-proven primary FSGS and in a large control group: the ACE insertion/deletion polymorphism in intron 16, the M235T mutation in the angiotensinogen gene, and the A1166C in the angiotensin II type 1 receptor gene (AT1R). Arab patients showed a greater tendency towards progressive renal disease than their Jewish counterparts (12 of 21 vs. 9 of 26, P = 0.05) and were less likely to achieve remission (3 of 21 vs. 11 of 26, P < 0.04), despite similar clinical presentation, medical management and follow-up. The RAS allele prevalence was similar among patients and controls of matching ethnic backgrounds, and no difference in allele frequency was found between Arabs and Jews. Homozygotes for the ACE insertion genotype (II) were significantly less likely to have progressive renal disease than patients with the other genotypes (ID and DD; 0 of 6 vs. 21 of 41; P < 0.022). The other RAS polymorphisms were not associated with variations in the clinical course of childhood FSGS. Homozygosity for the ACE insertion allele may have a protective effect in children with FSGS and can serve as a positive prognostic indicator at diagnosis. The D allele may exert a detrimental dominant effect on outcome. Neither the ACE gene polymorphism nor the other RAS polymorphisms studied are associated with disease prevalence. The AT1R and angiotensinogen gene polymorphisms are not associated with progression of renal disease in FSGS. Ethnic differences in the clinical course of the disease are not linked to these polymorphisms.

0 comments Cited 13 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: not found
Article: not found

Role of the Angiotensin Type 2 Receptor Gene in Congenital Anomalies of the Kidney and Urinary Tract, CAKUT, of Mice and Men

Agnes Fogo, John Brock, Tadashi Inagami … (1999)

0 comments Cited 12 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

ACE I/D gene polymorphism predicts renal damage in congenital uropathies.

R Brezinska, P Brodhag, Donald W. Brenner … (1999)

We investigated angiotensin converting enzyme gene (ACE I/D) polymorphism as a risk for progressive renal damage in congenital uropathies. The ACE I/D genotype was determined in 196 Caucasian patients with congenital uropathies and 163 individuals with no clinical or sonographic evidence of any urological malformations. The study group included patients with ureteropelvic junction obstruction (n=49), primary obstructive megaureter (n=19), primary vesicoureteral reflux (VUR) (n=67), and posterior urethral valves (n=27). Thirty-four patients were excluded because of additional diseases or insufficient follow-up. There was no difference in the ACE I/D distribution between children with uropathies and normal controls (II 16%, ID 56%. DD 28% vs. II 26%, ID 50%, DD 24%). Renal lesions were found in 99 of 162 children by ultrasonography, intravenous pyelography, and nuclear scans. In these children there was significant over-representation of the DD genotype (II 11%, ID 53%, DD 36%) compared with normals (P<0.005, X2=14.9) or with patients with uropathies but no renal lesions (II 23%, ID 62%, DD 15%, P<0.005, X2=14.9). Because ACE I/D has been linked with progressive deterioration of renal function, we evaluated a subset of patients with initially normal kidneys who developed radiographic renal lesions (n=28). Among these patients there was an even greater over-representation of the DD genotype (II 0%, ID 43%, DD 57%, P<0.001, X2=22.6) compared with patients with uropathies but no radiographic lesions. Multivariate analysis revealed that the DD genotype is a risk factor for parenchymal destruction, which was independent of time of diagnosis, surgical intervention, or urinary tract infection. This finding was particularly relevant in patients with VUR who constituted the majority with initially normal kidneys who developed radiographic damage (22/28). Indeed, the odds ratio of developing parenchymal damage with VUR was significantly increased if the individual had the DD genotype (4.2, 95% confidence interval 1.4-13.0). In conclusion the ACE I/D gene polymorphism is a risk factor for renal parenchymal damage in patients with congenital urological abnormalities and appears particularly relevant in children with VUR, where it is an independent predisposing factor.

0 comments Cited 8 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Journal

Journal ID (publisher-id): AJN

Journal ID (nlm-ta): Am J Nephrol

Journal ID (doi): 10.1159/issn.0250-8095

Title: American Journal of Nephrology

Publisher: S. Karger AG

ISSN (Print): 0250-8095

ISSN (Electronic): 1421-9670

Publication date Subscription-year: 2004

Publication date (Print): April 2004

Publication date (Electronic): 08 April 2004

Volume: 24

Issue: 2

Pages: 178-187

Affiliations

Department of Pediatrics, College of Medicine, Korea University, Seoul, Korea

Article

Publisher ID: 76620 Other ID: Am J Nephrol 2004;24:178–187

DOI: 10.1159/000076620

PubMed ID: 14764974

License:

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.