A genetic study of steroid-resistant nephrotic syndrome: relationship between polymorphism -173 G to C in the MIF gene and serum level MIF in children

Abstract

There is no satisfactory explanation as to why some nephrotic syndrome (NS) patients respond to glucocorticoids and others do not. The aim of this study was to investigate an association between single nucleotide polymorphism of the MIF gene -rs755622 and serum MIF concentrations in NS patients. During a period between November 2011 and September 2012, 120 consecutive children divided into three groups [healthy children, steroid-resistant nephrotic syndrome (SRNS) and steroid-sensitive nephrotic syndrome (SSNS)] were examined. Children were defined as healthy when they had a normal estimated glomerular filtration rate and spot urinary albumin creatinine ratio <150 μg/mg creatinine. SRNS was diagnosed in children who did not respond to the usual doses of steroids within 4 weeks of initiating treatment. SSNS patients were defined as those who had remission after usual doses of steroids. The genotype of -173 G to C polymorphism of the MIF gene was determined using polymerase chain reaction restriction fragment length polymorphism methods. Serum MIF concentration was measured using sandwich enzyme-linked immunosorbent assay. The allele frequency of the C allele was higher in SRNS compared with that of SSNS patients (P=0.025). There was a trend toward an association between genotypes and serum MIF disturbances. In conclusion, this study noted elevated circulating serum MIF levels and higher frequency of the C allele of the MIF gene in SRNS patients. The presence of the C allele implies an increased risk for steroid resistance.

Macrophage Migration Inhibitory Factor -173 G/C Polymorphism: A Global Meta-Analysis across the Disease Spectrum

“…We included this model in the analysis to determine if a strong influence of a single allele on disease was present, however, this was not the case. The localization of the polymorphism on the promoter sequence indicates that its biological significance is related to differences in the transcript expression levels (Matia-García et al, 2015 ; Ramayani et al, 2016 ; Bae and Lee, 2017 ), and this differences are better explained in an individual by genotypes than by alleles. The use of the allelic model duplicates the data available for analysis in comparison to genotypes, but does not provide useful information on the relation with disease, considering the nature of the polymorphism, and indicating that this model is not useful in our current analysis.…”

“…This polymorphism has been associated with the pathophysiology of arthritis, infections and inflammatory-related diseases (Donn et al, 2001 ; Baugh et al, 2002 ). The importance of this variant is due to its localization on the CpG island of the MIF promoter, where the G > C change generates an additional CpG motif and binding site for the transcription factor activator protein 4 (AP4) (Donn et al, 2001 ), which in turn increases the levels of both transcripts and protein (Matia-García et al, 2015 ; Ramayani et al, 2016 ; Bae and Lee, 2017 ).…”

Pharmacology and pharmacogenetics of prednisone and prednisolone in patients with nephrotic syndrome

“…The allele MIF-173*C (rs755622) is associated with higher serum MIF levels. Several studies have been conducted to investigate the potential role of this genetic polymorphism in the gene encoding for MIF in patients with nephrotic syndrome [ 71 , 79 – 81 , 104 , 105 ]. A meta-analysis conducted by Tong et al showed that the gene polymorphism rs755622 plays an important role in the risk of glucocorticoid resistance in patients with nephrotic syndrome [ 106 ].…”

Association Between Macrophage Migration Inhibitory Factor -173 G>C Gene Polymorphism and Childhood Idiopathic Nephrotic Syndrome: A Meta-Analysis

“…One study did not explicitly classify INS into SSNS and SRNS according to steroid responsiveness (13), so we excluded it in the meta-analysis of MIF -173 G>C polymorphism and steroid responsiveness. In the other six studies, three studies provided a specific definition of steroid resistance (14)(15)(16). According to the NOS scale, all the included studies were considered to be of high quality (score ≥ 6).…”