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

Frishberg, Yaacov; Becker-Cohen, Rachel; Halle, David; Feigin, Elad; Eisenstein, Bella; Halevy, Raphaël; Lotan, Danny; Juabeh, Isam; Ish-Shalom, N; Magen, Daniella; Shvil, Yigal; Sinai-Treiman, Levana; Drukker, Alfred

doi:10.1046/j.1523-1755.1998.00218.x

Cited by 51 publications

(70 citation statements)

References 37 publications

(41 reference statements)

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“…Different results have been reported from the studies of ACE I/D polymorphism in children with NS and other renal diseases. 4,7,8,27,28,[35][36][37][38] In these studies, it was reported that the D polymorphism of ACE gene is a risk factor for the progression to ESRD in patients with FSGS, IgA nephropathy, hypertension and diabetic nephropathy. But it was also reported that no association was detected between the polymorphism of both AT 1 R and AGT and disease progression.…”

Section: Discussionmentioning

confidence: 99%

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Effects of Genetic Polymorphisms of the Renin-Angiotensin System in Children with Nephrotic Syndrome

Tabel

Berdelı

Mır

et al. 2005

J Renin Angiotensin Aldosterone Syst

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Background. The renin-angiotensin system (RAS) has been considered to be responsible for the pathogenesis or progression of many diseases which may or may not be related to kidney. Genetic polymorphisms of the various components of the RAS have been associated with differences in the clinical course of several disease states in adults and children. Objectives. The purpose of our study was to investigate RAS gene polymorphisms in patients with steroid resistant primary focal segmental glomerulosclerosis (FSGS) and nephrotic syndrome responding to steroid therapy. Furthermore, we aimed to investigate whether there was an association between polymorphic alleles and responses to steroid therapy, the degree of renal dysfunction, and prevalence of end-stage renal disease (ESRD). Material and methods. One hundred and fifty-eight children with the diagnosis of nephrotic syndrome were recruited from the Nephrology unit in the Department of Paediatrics of Ege University. Forty-nine of them were classified as renal biopsy-proven FSGS and 102 patients were considered to have response to steroid treatment. Renal functional impairment was detected in 19 subjects with FSGS and end-stage renal insufficiency in 13 patients. The control group consisted of 287 healthy adult subjects. Angiotensin-converting enzyme (ACE), angiotensin II type 1 receptor (AT 1 R) and angiotensinogen (AGT) gene polymorphisms were determined by the polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) technique. Statistical significance was regarded as p<0.05. Results. There were no statistically significant differences for the C allele of AT 1 R or the T allele of AGT genes between the children with nephrotic syndrome and control group, but on the other hand statistically significant differences were detected for D allele of ACE gene. There was no significant relationship detected between the D allele of ACE, the C allele of AT 1 R or the T allele of AGT genes and response to steroid therapy, extent of renal dysfunction and the progression to ESRD. However, there was a significant relationship

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Section: Discussionmentioning

confidence: 99%

“…6 RAS-related studies in children have particularly focused on nephrotic syndrome (NS) patients. 7,8 The polymorphism 138 …”

Section: Introductionmentioning

confidence: 99%

Effects of Genetic Polymorphisms of the Renin-Angiotensin System in Children with Nephrotic Syndrome

Tabel

Berdelı

Mır

et al. 2005

J Renin Angiotensin Aldosterone Syst

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“…Similarly, a study from Israel reported that they achieved remission in two thirds of children with the II genotype, but in only 24% of children with the DD and ID genotype. 12 They concluded that ACE genotype interfered with steroid response in the patients with FSGS. Lee and his colleagues reported in a Korean population a steroid response in 1/8 patients with the DD genotype and 5/18 patients with the other genotypes.…”

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Effect of angiotensin-converting enzyme gene insertion/deletion polymorphism on steroid resistance in Egyptian children with idiopathic nephrotic syndrome

Saber-Ayad

Sabry

AbdElLatif

et al. 2010

J Renin Angiotensin Aldosterone Syst

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Introduction. The presence of the deletion (D) allele in the angiotensin-converting enzyme (ACE) gene has been reported as a probable genetic risk factor for idiopathic nephrotic syndrome (INS), but its role in determining resistance to steroid therapy remains to be evaluated. Methods. Fifty-one patients were enrolled in the study and received oral steroids. The pattern of response to steroid therapy was determined. A group of 50 healthy adults served as a control group. The genotypes for ACE insertion (I)/D polymorphism were analysed using a PCR-based method. Results. Twenty patients were steroid sensitive (SS) and 31 were non-SS. The presence of hypertension at presentation was significantly related to steroid unresponsiveness. Among the SS group, the frequencies of the II, ID, and DD genotypes of the ACE gene were 20% (n=4), 65% (n=13), and 15% (n=3), respectively, while the frequencies among the non-SS group were 19.4% (n=6), 74.2% (n=23), and 6.5% (n=2), respectively. The differences between the two groups were not statistically significant (Chi square=0.59). Conclusion. The current study on Egyptian children with INS reveals no association between the ACE gene I/D polymorphism and clinical parameters, histological findings, and steroid resistance.

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“…It has been found that homozygosity for the ACE I allele may have a protective effect in children with FSGS and can serve as a positive prognostic indicator at diagnosis, while the D allele may exert a detrimental dominant effect on outcome. 21 Recently, it has also been shown that the DD genotype may be a risk factor for the development of progressive renal impairment in children with FSGS. 22 Another study demonstrated that ACE I/D polymorphism does not contribute to the steroid resistance, but carriers of I/D genotype introduce 2.8-fold risk for NS.…”

Section: Discussionmentioning

confidence: 99%

DD Genotype of ACE Gene in Boys: May it be a Risk Factor for Minimal Change Nephrotic Syndrome?

2011

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It has been shown that angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism affects the circulating and cellular levels of ACE and may be a risk factor in several renal diseases. We analyzed the association of ACE gene I/D polymorphism with the clinical presentation of minimal change nephrotic syndrome (MCNS) in a Turkish child population. This study consisted of 97 children with MCNS and 144 healthy controls. Genotyping of ACE gene was performed using polymerase chain reaction (PCR). The distributions of ACE genotypes were II in 13%, ID in 49%, and DD in 38% in patient group, and 9%, 49%, and 42% in control group, respectively. The frequency of the D allele was 63% and that of the I allele was 37% in patients. There were no relevant differences in the allele frequencies and genotypes of ACE I/D polymorphism between patients and controls. However, DD genotype was higher in boys in children with MCNS (78.4%. vs. 50.0%, p = 0.004). The frequencies of DD genotype and D allele in boys were 7.25 and 2.56 times higher than II genotype and I allele in the patient group, respectively. We suggest that DD genotype in boys may be one of the risk factors for MCNS.

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

Cited by 51 publications

References 37 publications

Effects of Genetic Polymorphisms of the Renin-Angiotensin System in Children with Nephrotic Syndrome

Effects of Genetic Polymorphisms of the Renin-Angiotensin System in Children with Nephrotic Syndrome

Effect of angiotensin-converting enzyme gene insertion/deletion polymorphism on steroid resistance in Egyptian children with idiopathic nephrotic syndrome

DD Genotype of ACE Gene in Boys: May it be a Risk Factor for Minimal Change Nephrotic Syndrome?

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