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Objective: Angiotensin converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism influence the circulating and cellular levels of ACE and has been shown to be a risk factor in a number of diseases including IgA nephropathy. We have investigated the association of ACE gene I/D polymorphism with the clinical presentation of idiopathic nephrotic syndrome (INS) in Kuwaiti children. Materials and methods: The genotypes for ACE gene I/D polymorphism were determined in 102 subjects (54 INS cases and 48 healthy controls) using a PCR method. Results: The distribution of DD, ID and II genotypes was 70%, 20% and 10% in INS cases compared with 52%, 46% and 2% in the controls. The mean age of onset of the disease was significantly lower in the INS cases with DD genotype (37 months) compared with cases with II genotype (65 months, p < 0.05). The clinical manifestation of the disease was considerably severe in cases with DD genotypes compared with cases having ID and II genotypes. The INS cases with DD genotype also showed a significantly higher incidence of steroid sensitivity and steroid dependence. Seventy-three per cent of the INS cases with minimal change lesion had a DD genotype. Also 70% of the cases which needed cytotoxic drugs had DD genotype. Conclusion: Our data suggest an association of the D-allele of the ACE gene I/D polymorphism with the clinical manifestation of INS in Kuwaiti Arab children. [ABSTRACT FROM AUTHOR]