Key result
ACE gene DD genotype and D allele linked to idiopathic nephrotic syndrome and steroid resistance.
Why the study?
The role of ACE insertion/deletion gene polymorphism in idiopathic nephrotic syndrome has shown conflicting results across ethnic groups, and its impact remained unexplored in Egyptian children.
Is the ACE gene I/D polymorphism associated with disease susceptibility, steroid response, and outcomes in Egyptian children with idiopathic nephrotic syndrome?
Is the ACE gene I/D polymorphism associated with disease susceptibility, steroid response, and outcomes in Egyptian children with idiopathic nephrotic syndrome?
The ACE gene DD genotype and D allele are associated with increased susceptibility to idiopathic nephrotic syndrome, steroid resistance, and worse renal outcomes in Egyptian children.
Should not yet change practice in Egyptian children with idiopathic nephrotic syndrome; extends prior ACE I/D associations but remains hypothesis-generating.
Purpose: Detecting the genetic etiology of idiopathic nephrotic syndrome (INS) in different ethnic groups, especially in steroid-resistant subjects, is currently essential for individualized management, predicting prognosis, and family counseling. The angiotensin-converting enzyme (ACE) insertion (I)/deletion (D) gene polymorphism has been studied for its possible role in INS in different ethnic groups with conflicting results reported. This study was carried out to explore the possible role of ACE I/D polymorphism in disease susceptibility, steroid response, and outcome in Egyptian children with INS. Subjects and Methods: ACE gene I/D polymorphism genotypes and allele frequencies were explored in 86 children with INS versus 140 healthy controls using polymerase chain reaction and examined in different disease phenotypes and pathological variants. Results: Thirty-sex patients were steroid resistant, and 20 had focal segmental glomerulosclerosis (FSGS). The DD genotype and D allele were significantly more frequent in patients compared to controls ( P < 0.001 for both) and in steroid-resistant compared to steroid-sensitive subjects ( P = 0.004 and 0.003, respectively). Furthermore, patients with FSGS displayed a higher rate of DD genotype ( P = 0.04) compared to other pathological variants. DD genotype was also more frequent in patients with hypertension compared to non-hypertensive subjects ( P = 0.03) and also in patients who progressed to renal impairment ( P = 0.04). Conclusion: The ACE gene DD genotype and D allele can be considered as risk factors for INS susceptibility and significant phenotype modifiers regarding the presentation, pathology, response to steroids, and renal survival in Egyptian children.
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Hammad et al. (2026) studied this question. The ACE gene DD genotype and D allele were significantly more frequent in Egyptian children with idiopathic nephrotic syndrome (P<0.001) and in those with steroid resistance (P=0.004).
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