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

Abstract

Glomerular diseases (GNs) are responsible for approximately 20% of chronic kidney diseases. Glucocorticoid receptor gene (<i>NR3C1</i>) 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 <i>NR3C1</i> 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 (<i>p</i> = 0.026); a significant association of rs17209237 with eGFR reduction after follow-up period in all patients with GNs (<i>p</i> = 0.021) and with the degree of proteinuria after 1 year of therapy in all patients with a glomerulopathy (<i>p</i> = 0.013) and IgAN (<i>p</i> = 0.021); and in the same groups treated with steroids (<i>p</i> = 0.021; <i>p</i> = 0.012). We also observed the association between rs41423247 and IgAN histopathologic findings (<i>p</i> = 0.012). In conclusion, our results indicate that <i>NR3C1</i> polymorphisms may influence treatment susceptibility and clinical outcome in IgAN and MN.