OBJECTIVE: Previous studies have shown that the reduced glucocorticoid (GC) sensitivity is associated with the mutations of glucocorticoid receptor (GCR) in patients with acute lymphocytic leukemia or with lupus nephritis. It has not been confirmed whether GC-resistance is the result of abnormal function of GCR induced by the alteration of GCR gene in children with primary nephrotic syndrome (PNS). The purpose of this study is to investigate the correlation between GC-resistance and the polymorphisms of GCR in DNA-binding domain and hormone-binding domain in children with PNS. METHODS: DNA was isolated from peripheral blood leukocytes in 100 children with PNS (44 with GC-sensitive, 56 with GC-resistance) and 100 healthy controls and each exon of the DNA-binding domain and hormone binding domain of GCR was amplified by the polymerase chain reaction (PCR). Single-strand conformation polymerase (SSCP) analysis of the PCR products was carried out for screening polymorphisms. DNA fragments displaying an abnormal migration pattern during SSC analysis were subjected to direct sequencing. RESULTS: PCR-SSCP analysis in all of the PCR products from the GC-resistance and GC-sensentivity cases did not display an abnormal DNA fragment migration pattern. Polymorphism of GCR in neither the DNA-binding domain nor the hormone-binding domain was found. CONCLUSIONS: There is no correlation between GC-resistance and the polymorphisms of GCR in DNA-binding domain and hormone-binding in children with PNS.