ACE gene insertion/deletion polymorphism in childhood idiopathic nephrotic syndrome

Abstract

The aim of this study was to determine the distribution of angiotensin converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism, and its effects on clinical, laboratory, histological findings, treatment responses and progression to end-stage renal disease in childhood idiopathic nephrotic syndrome (NS). 227 children diagnosed with idiopathic NS were included in the study. Eighty-three of patients were steroid resistant and 77 of patients were focal segmental glomerulosclerosis. The control group was consisted of 287 unrelated healthy adult volunteers. ACE gene I/D polymorphism were analyzed by using PCR based method. In the entire group of children with NS, the frequencies of the II, ID, and DD genotypes of ACE gene were 13.7%, 38.3% and 48%, respectively. D allele frequency was higher in NS group than control group (0.67 vs. 0.56, p=0.001). Percentage of frequent relapser patients was found more frequently in ID or DD genotype (38.7%) than II genotype (15%) when only steroid sensitive patients were evaluated (p=0.045). The D-allele frequency was 0.65, 0.69 and 0.68 respectively in focal segmental glomerulosclerosis, biopsy proven minimal change and entire minimal change group (p>0.05) and 0.69 and 0.64 respectively in steroid sensitive and resistant groups (p>0.05). D allele frequency was not significantly different in patients with or without end-stage renal disease (0.64 vs. 0.67 respectively, p>0.005) when 115 patients who were at least five year follow-up were evaluated. The D allele frequency was higher in NS patients than healthy controls and DD or ID genotype was related with frequent relapses. ACE gene I/D polymorphism was not important in laboratory and histological findings and progression of the disease in children with NS.

Association of angiotensin converting enzyme insertion/deletion gene polymorphism with idiopathic nephrotic syndrome susceptibility in children: a meta-analysis

“…Patients in four investigations [17][18][19][20] suf fered from NS but those studies did not mention whether the patients were suffering from INS or NS, and those investigations were excluded from our metaanalysis. Nine studies 12,13,[21][22][23][24][25][26][27] were identified for the analysis of the asso ciation between ACE I/D gene polymorphism and INS sus ceptibility in our final review ( Figure 1) and all the studies were performed in children. In those nine reports, three 21 presented the diagnostic criteria for INS in their studies, which was consistent with the definition of INS in our study, and other six reports only mentioned that the patients recruited into their studies were suffering from INS but did not show the definition of INS in their reports.…”

“…In those nine reports, three 21 presented the diagnostic criteria for INS in their studies, which was consistent with the definition of INS in our study, and other six reports only mentioned that the patients recruited into their studies were suffering from INS but did not show the definition of INS in their reports. Six studies 13,[21][22][23][24]27 were conducted in Asians, one investigation 25 was performed in Caucasian children and two studies 12,26 were conducted in Africans. Eight studies were published in English and one investigation 21 was published in Chinese.…”

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

“…23 The genetic polymorphism of ACE gene I/D polymorphism in children with idiopathic nephrotic syndrome (INS) as well as its relationship with patients' clinical response to steroid therapy has been investigated in several studies. Serdaroglu et al 24 found that the D allele frequency was higher in NS patients than healthy controls, and DD or ID genotype was related with frequent relapses, while ACE gene I/D polymorphism was not important in laboratory and histological findings and in the progression of disease in children with NS.…”

A meta-analysis of the association between angiotensin-converting enzyme insertion/deletion gene polymorphism and steroid-sensitive nephrotic syndrome in children

“…4 In Asian children, Serdaroglu et al 7 8 found that the DD genotype was more frequent in the SSNS group than that in normal control group in Turkish children. Al-Eisa et al 9 conducted a study in Kuwaiti Arab Children and observed that the INS cases with DD genotype also showed a significantly higher incidence of steroid sensitivity.…”

“…4 Most children with INS respond to corticosteroid treatment (SSNS), and about 10% of children with INS are mainly steroid-resistant (SRNS). 5 Angiotensin-converting enzyme (ACE) insertion/ deletion (I/D) gene polymorphism, correlating with circulating and cellular ACE concentration, 6,7 has been implicated in the aetiology of SSNS and has been investigated in numerous epidemiological studies. However, the available evidence reported to date is weak, due to the sparseness of data or disagreements among the reported investigations.…”