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      Association between angiotensin converting enzyme gene insertion/deletion polymorphism and renal scar risk in children vesicoureteral reflex: a reappraise meta-analysis

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          Abstract

          Vesicoureteral reflex(VUR) is a common disease in children. Some studies indicated that the angiotensin converting enzyme ( ACE) gene insertion/deletion (I/D) polymorphism associated with the renal scar in VUR, but not all researchers agreed with it. To clarify the effect of ACE I/D polymorphism on renal scar risk in children with VUR, we performed the present meta-analysis. PubMed, CNKI, CBM, and Embase databases were searched for studies that examined the relationship between ACE I/D polymorphism and renal scar risk in children with VUR. The Stata 12.0 software was used for statistical analyses. 11 case-control studies with 1,032 VUR patients were analyzed. The results showed that the DD genotype and D allele were associated with renal scar risk in overall VUR patients, DD vs. DI + II: OR = 1.61, 95% CI = 1.04–2.49, P = 0.03; DD vs. II: OR = 1.78, 95% CI = 1.20–2.65, P < 0.01; D vs. I: OR = 1.38, 95% CI = 1.02–1.86, P = 0.04. Similar results were revealed in Turks, but not in Caucasians and Asians. Our meta-analysis indicated that the ACE DD genotype may increase the risk of renal scar in children with VUR.

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          Evidence, from combined segregation and linkage analysis, that a variant of the angiotensin I-converting enzyme (ACE) gene controls plasma ACE levels.

          F A Cambien, P Corvol, F Soubrier … (1992)
          The hypothesis of a genetic control of plasma angiotensin I-converting enzyme (ACE) level has been suggested both by segregation analysis and by the identification of an insertion/deletion (I/D) polymorphism of the ACE gene, a polymorphism contributing much to the variability of ACE level. To elucidate whether the I/D polymorphism was directly involved in the genetic regulation, plasma ACE activity and genotype for the I/D polymorphism were both measured in a sample of 98 healthy nuclear families. The pattern of familial correlations of ACE level was compatible with a zero correlation between spouses and equal parent-offspring and sib-sib correlations (.24 +/- .04). A segregation analysis indicated that this familial resemblance could be entirely explained by the transmission of a codominant major gene. The I/D polymorphism was associated with marked differences of ACE levels, although these differences were less pronounced than those observed in the segregation analysis. After adjustment for the polymorphism effects, the residual heritability (.280 +/- .096) was significant. Finally, a combined segregation and linkage analysis provided evidence that the major-gene effect was due to a variant of the ACE gene, in strong linkage disequilibrium with the I/D polymorphism. The marker allele I appeared always associated with the major-gene allele s characterized by lower ACE levels. The frequency of allele I was .431 +/- .025, and that of major allele s was .557 +/- .041. The major gene had codominant effects equal to 1.3 residual SDs and accounted for 44% of the total variability of ACE level, as compared with 28% for the I/D polymorphism.(ABSTRACT TRUNCATED AT 250 WORDS)
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            EAU guidelines on vesicoureteral reflux in children.

            Serdar Tekgul, Hubertus Riedmiller, Piet Hoebeke … (2012)
            Primary vesicoureteral reflux (VUR) is a common congenital urinary tract abnormality in children. There is considerable controversy regarding its management. Preservation of kidney function is the main goal of treatment, which necessitates identification of patients requiring early intervention. To present a management approach for VUR based on early risk assessment. A literature search was performed and the data reviewed. From selected papers, data were extracted and analyzed with a focus on risk stratification. The authors recognize that there are limited high-level data on which to base unequivocal recommendations, necessitating a revisiting of this topic in the years to come. There is no consensus on the optimal management of VUR or on its diagnostic procedures, treatment options, or most effective timing of treatment. By defining risk factors (family history, gender, laterality, age at presentation, presenting symptoms, VUR grade, duplication, and other voiding dysfunctions), early stratification should allow identification of patients at high potential risk of renal scarring and urinary tract infections (UTIs). Imaging is the basis for diagnosis and further management. Standard imaging tests comprise renal and bladder ultrasonography, voiding cystourethrography, and nuclear renal scanning. There is a well-documented link with lower urinary tract dysfunction (LUTD); patients with LUTD and febrile UTI are likely to present with VUR. Diagnosis can be confirmed through a video urodynamic study combined with a urodynamic investigation. Early screening of the siblings and offspring of reflux patients seems indicated. Conservative therapy includes watchful waiting, intermittent or continuous antibiotic prophylaxis, and bladder rehabilitation in patients with LUTD. The goal of the conservative approach is prevention of febrile UTI, since VUR will not damage the kidney when it is free of infection. Interventional therapies include injection of bulking agents and ureteral reimplantation. Reimplantation can be performed using a number of different surgical approaches, with a recent focus on minimally invasive techniques. While it is important to avoid overtreatment, finding a balance between cases with clinically insignificant VUR and cases that require immediate intervention should be the guiding principle in the management of children presenting with VUR. Copyright © 2012 European Association of Urology. Published by Elsevier B.V. All rights reserved.
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              Association between genetic polymorphism of the angiotensin-converting enzyme and diabetic nephropathy: a meta-analysis comprising 26,580 subjects.

              Furu Wang, Xingjiang Cao, Xiangyong Fan … (2012)
              The effect of angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism on risk of diabetic nephropathy (DN) is still conflicting. The present meta-analysis was performed to evaluate the overall risk of this polymorphism associated with DN in different groups. A predefined search was performed on 14,108 DN cases and 12,472 controls from 63 published studies by searching electronic databases and reference lists of relevant articles. In this meta-analysis, we found a significant association between the ACE I/D polymorphism and the risk of DN for all genetic models (ID versus II: odds ratio [OR] = 1.12, 95% confidence interval [CI] 1.02-1.24; DD versus II: OR = 1.27, 95% CI 1.13-1.44; allele contrast: OR = 1.15, 95% CI 1.08-1.23; dominant model: OR = 1.18, 95% CI 1.07-1.31; and recessive model: OR = 1.18, 95% CI 1.08-1.30, respectively). In stratified analysis by ethnicity and DM type, we further found that the Asian group with type 2 diabetes mellitus (T2DM) showed a significant association for all genetic models (ID versus II: OR = 1.25, 95% CI 1.07-1.47; DD versus II: OR = 1.57, 95% CI 1.24-1.98; allele contrast: OR = 1.30, 95% CI 1.15-1.46; dominant model: OR = 1.37, 95% CI 1.10-1.69; and recessive model: OR = 1.34, 95% CI 1.15-1.56, respectively). Our study suggested that the ACE I/D polymorphism may contribute to DN development, especially in the Asian group with T2DM.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Sci Rep
                Journal ID (iso-abbrev): Sci Rep
                Title: Scientific Reports
                Publisher: Nature Publishing Group
                ISSN (Electronic): 2045-2322
                Publication date (Electronic): 10 August 2016
                Publication date Collection: 2016
                Volume: 6
                Electronic Location Identifier: 31243
                Affiliations
                [1 ]Evidence-Based Medicine Center, Xiangyang Hospital, Hubei University of Medicine , Xiangyang 441000, P.R. China
                [2 ]Department of Urology, Zhongnan Hospital of Wuhan University , Wuhan 430071, P.R. China
                [3 ]Center for Evidence-Based Medicine and Translational Medicine, Zhongnan Hospital of Wuhan University , Wuhan 430071, P.R. China
                [4 ]Center for Evidence-Based Medicine and Translational Medicine, Wuhan University , Wuhan 430071, P.R. China
                [5 ]Department of Pediatrics, Shiyan People’s Hospital, Hubei University of Medicine , Shiyan 442000, P.R. China
                Author notes
                [*]

                These authors contributed equally to this work.

                Article
                Publisher Item ID: srep31243
                DOI: 10.1038/srep31243
                PMC ID: 4978959
                PubMed ID: 27506878
                SO-VID: d3ab1b7e-7d75-4dda-9af4-f6d844244f62
                Copyright © Copyright © 2016, The Author(s)
                License:

                This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

                History
                Date received : 21 March 2016
                Date accepted : 15 July 2016
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