MDR-1 gene polymorphisms in steroid-responsive versus steroid-resistant nephrotic syndrome in children.

Background. The putative genetic regulation of multidrug resistance gene-1 (MDR-1) gene expression and P-glycoprotein function has not yet been clearly delineated in patients with nephrotic syndrome (NS). We undertook this study to examine the distribution of three most frequent MDR-1 exonic polymorphisms G3435C, G2677T/A and C1236T in patients with NS and control children to investigate their usefulness as markers of responsiveness of the disease to steroids.Methods. Two hundred and sixteen children with NS and 216 healthy controls were genotyped for three exonic MDR-1 polymorphisms (G3435C, G2677T/A and C1236T) by using the polymerase chain reaction–restriction fragment length polymorphism technique. The frequency distribution of genotypes/alleles was compared between patients with NS and controls and also between steroid-sensitive NS (SSNS) and steroid-resistant NS (SRNS) patients.Results. Of the total 216 cases of NS (median age of onset 5 years, 165 males), 137 had SSNS, and 79 had SRNS. Homozygous mutants of C3435T (TT versus CC, P = 0.034) and G2677T/A (TT + AA versus GG), P = 0.030) were significantly higher in patients with NS compared to controls. The frequency distribution of homozygous mutant TT + AA compared to wild genotype GG was significantly higher in SRNS than SSNS patients (P = 0.011) for G2677T/A, while the mutant genotypes for C3435T and C1236T were not different between SRNS and SSNS patients. The combination-bearing mutant genotype either of C3435T or G2677T/A exhibited a significantly higher frequency of mutant genotypes distribution in SRNS patients. MDR-1 haplotypes did not differ significantly between SSNS and SRNS patients.Conclusions. Patients with NS carrying homozygous mutants of single nucleotide polymorphism (SNP) G2677T/A are prone to develop SRNS. The synergistic effect of mutant genotypes of SNPs G2677T/A and C3435T in different combinations increase the risk of developing steroid resistance in patients with NS. [ABSTRACT FROM PUBLISHER]