Molecular analysis of glucocorticoid receptor gene single nucleotide polymorphisms N363S and BclI in adult patients with nephrotic syndrome

Abstract

Nephrotic syndrome (NS) is a glomerular disease characterized by severe proteinuria, hypoalbuminemia, hypercholesterolemia, and edema. The reason for proteinuria in NS is the deficiency in the structure or function of Glomerule arterioles. Glucocorticoid (GC) therapy is a selective treatment strategy for patients with nephrotic syndrome. Due to the lack of positive response of all patients to GC treatment and resistance to GC therapy, as well as the dependency of biological effects of GC on cytoplasmic receptors of glucocorticoids (GR) and the role of gene encoding on these receptors (NR3C1), on GR tendency to glucocorticosteroids, In this study, we investigated that the resistance polymorphisms to the steroid of NR3C1 gene in patients with nephrotic syndrome and also, their relationship with patients' clinical parameters. This lack of response may increase kidney failure. Therefore; resistance to Glucocorticoids (GC) is the main challenge for the treatment of Nephrotic syndrome patients. In recent years the relationship between Polymorphisms that are the receptor of GC, process of illness and prognosis of Nephrotic syndrome are investigated. According to the impact of Polymorphisms' genes (NR3C1) as a coding gene of Glucocorticoids receptor ( GR) on tendency to Glucocorticoids receptor, variance and polymorphism of NR3C1 gene can play an important role in the response to treatment with glucocorticoids . NR3C1 gene can affect the regulation of many biological functions, including response to GC, and its functional variability may be important in response to GC therapy. Some of these polymorphisms may be considered as pharmacogenetic markers. Therefore, our aim in this study is to investigate Steroid resistance polymorphisms in patients with nephrotic syndrome. Methods: For this case-control study, blood samples were collected from 53 patients with nephrotic syndrome referred to Imam Reza (AS) Hospital in Tabriz who were selected based on biopsy results and also, 30 healthy individuals with nephrotic syndrome and blood collection. Then the blood DNA of the samples was extracted and by the RFLP-PCR technique, the single nucleotide polymorphisms of ER22 / 23EK and GR-9β of NR3C1 gene were determined and compared between the control and patient groups Results: Based on the results of gene sequencing, no significant difference was observed between the frequency of ER22 / 23EK and GR-9β polymorphisms of the NR3C1 gene in the patient group including nephrotic syndrome, membranous glomerulonephritis, and ovarian disease and the control group. Conclusion: According to our results, it can be concluded that steroid-resistant NR3C1 gene polymorphisms including ER22 / 23EK and GR-9β mononuclear polymorphisms may not affect steroid resistance and glucocorticoid therapy, which needs further study.