Multi-drug resistance-1 gene polymorphisms in nephrotic syndrome: Impact on susceptibility and response to steroids |
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Authors: | Doaa M Youssef Tarek A Attia Amal S El-Shal Fawzya A Abduelometty |
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Institution: | 1. Pediatrics Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt;2. Medical Biochemistry Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt |
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Abstract: | BackgroundRole of multidrug resistance-1 (MDR-1) gene polymorphisms has not been clarified in nephrotic syndrome (NS). Additionally, researchers studied several genetic polymorphisms to explain their influence on different patients' responses to steroid; however the data were inconsistent. Therefore, we aimed to investigate the association of MDR-1 gene polymorphisms C1236T, G2677T/A, C3435T] and haplotypes with susceptibility to childhood nephrotic syndrome, and whether they influence steroid response.MethodsWe detected MDR-1 gene polymorphisms using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) in 138 NS patients and 140 age and sex matched healthy children.ResultsThe frequencies of MDR1 G2677T/A GT, GA, TT + AA genotypes or T allele, MDR1 C3435T TT genotype, and T allele genotype frequencies were significantly increased in NS group. While no significant differences were observed in distributions of C1236T genotypes or allele between NS patients and healthy children. Moreover, steroid non-responder NS patients had significantly higher frequencies of MDR1 G2677T/A GT, GA, and TT + AA genotypes than steroid responsive NS patients. We observed also that NS patients with age less than 6 years old had increased frequencies of MDR1 G2677T/A GT, GA, TT + AA genotypes or T allele MDR1 C3435T CT, TT genotypes and T allele. Interestingly the frequency of the TGC haplotype of MDR1 was lower in the initial steroid responders than in non-responders NS patients. On the contrary, there were no any association between the MDR1 haplotypes with NS susceptibility and they did not influence renal pathological findings.ConclusionOur data suggested that MDR1 C3435T or G2677T/A gene polymorphisms are risk factors of increased susceptibility, earlier onset of NS, and steroid resistance. |
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Keywords: | MDR-1 multidrug resistance-1 NS nephrotic syndrome PCR-RFLP polymerase chain reaction restriction fragment length polymorphism MCN minimal change nephropathy GC glucocorticoids FSGS focal segmental glomerulosclerosis SNPs single nucleotide polymorphisms SS steroid sensitive SR steroid resistant SD steroid-dependent ANOVA One way analysis of variance INS idiopathic nephrotic syndrome |
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