NR3C1 Glucocorticoid Receptor Gene Polymorphisms Are Associated with Membranous and IgA Nephropathies.

Michał Pac,Aleksandra Wyczałkowska-Tomasik,Natalia Krata,Beata Kaleta,Leszek Pączek,Barbara Moszczuk,Witold Rudnicki,Bartosz Foroncewicz,Krzysztof Mucha

doi:10.3390/cells10113186

Abstract

Glomerular diseases (GNs) are responsible for approximately 20% of chronic kidney diseases. Glucocorticoid receptor gene (NR3C1) single nucleotide polymorphisms (SNPs) are implicated in differences in predisposition to autoimmunity and steroid sensitivity. The aim of this study was to evaluate the frequency of the NR3C1 SNPs—rs6198, rs41423247 and rs17209237—in 72 IgA nephropathy (IgAN) and 38 membranous nephropathy (MN) patients compared to 175 healthy controls and to correlate the effectiveness of treatment in IgAN and MN groups defined as a reduction of proteinuria <1 g/24 h after 12 months of treatment. Real-time polymerase chain reactions and SNP array-based typing were used. We found significant rs41423247 association with MN (p = 0.026); a significant association of rs17209237 with eGFR reduction after follow-up period in all patients with GNs (p = 0.021) and with the degree of proteinuria after 1 year of therapy in all patients with a glomerulopathy (p = 0.013) and IgAN (p = 0.021); and in the same groups treated with steroids (p = 0.021; p = 0.012). We also observed the association between rs41423247 and IgAN histopathologic findings (p = 0.012). In conclusion, our results indicate that NR3C1 polymorphisms may influence treatment susceptibility and clinical outcome in IgAN and MN.

Highlights

Glomerular diseases (GNs) are responsible for approximately 20% of chronic kidney diseases around the world [1]
We decided to study NR3C1 polymorphisms in IgA nephropathy (IgAN), because, it is classified as the rare disease, it constitutes a serious problem for public health worldwide
We demonstrated that the GC genotype of the rs41423247 NR3C1 polymorphism was less frequent in the membranous nephropathy (MN) patients than in healthy controls and IgAN

Summary

Introduction

Glomerular diseases (GNs) are responsible for approximately 20% of chronic kidney diseases around the world [1]. IgA nephropathy (IgAN) and membranous nephropathy (MN) are among the dominant GNs in the adult population. Recent years have brought new insights into a molecular background of GNs, especially in the field of -omics (genomics, transcriptomics, and proteomics) [2,3,4,5,6,7]. These discoveries revealed pathophysiologic mechanisms, which could be helpful in the development of biomarkers and targeted therapy in the future.

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