title: Polymorphic variants of MIF gene and prognosis in steroid therapy in children with idiopathic nephrotic syndrome.
abstract: Nephrotic syndrome (NS) is the most common reason of proteinuria in children and can be caused by the pathology of renal glomeruli. Steroid therapy is typically used in this disorder. It has been shown that MIF is a cytokine which counteracts the immunosuppressive properties of glucocorticoids. The aim of this study was looking for a correlation between MIF polymorphisms and genetic susceptibility to steroid resistance in children with INS (Idiopathic NS).
  
  
  METHODS
  The study was performed in 71 patients with INS including SRNS (steroid resistance nephrotic syndrome) (41) and SSNS (steroid sensitive nephrotic syndrome) (30) and in 30 control subjects. We employed Sanger sequencing and capillary electrophoresis. Linkage disequilibrium was made using Haploview and PHASE.
  
  
  RESULTS
  We didn't observe a statistical significance between SNPs detected in patients with INS and controls. Our studies revealed statistical significance for two polymorphisms: rs2070767C > T and rs2000466T > G between patients with SRNS and SSNS. The results for rs34383331T > A are close to being statistically significant. Statistical significance was revealed for CATT5/CATT6 genotype in SRNS group vs SSNS group (OR=4.604, 95%CI=1.356-15.632, p=0.0168). We found that the frequency of 5/X-CATT genotype compared with X/X-CATT genotype was significantly higher in SRNS patients vs SSNS (OR=3.167, 95%CI=1.046-9.585, p=0.0426). In linkage disequilibrium analysis we didn't show involvement in susceptibility to INS and steroid sensitive phenotype.
  
  
  CONCLUSIONS
  Our results suggest that the role of MIF polymorphisms in the susceptibility to positive response to steroid therapy is still unresolved. It indicates that MIF may be involved in indirect and complex molecular mechanisms of steroid activity in hormone-dependent metabolic pathways in children with INS. Because of ambiguous findings, pleiotropic features of this cytokine require that more research should be undertaken.
authors.affiliation: Department of Histology and Embryology, Poznan University of Medical Sciences, Poland.
authors.forename: Monika
authors.initials: M
authors.lastname: Świerczewska
authors.affiliation: Department of Pediatric Cardiology and Nephrology, Poznan University of Medical Sciences, Poland.
authors.forename: Danuta
authors.initials: D
authors.lastname: Ostalska-Nowicka
authors.affiliation: Department of Histology and Embryology, Poznan University of Medical Sciences, Poland and Department of Anatomy, Poznan University of Medical Sciences, Poland.
authors.forename: Bartosz
authors.initials: B
authors.lastname: Kempisty
authors.affiliation: Laboratory of Molecular and Cell Biology, Department of Pulmonology, Pediatric Allergy and Clinical Immunology, Poznan University of Medical Sciences, Poland.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Szczepankiewicz
authors.affiliation: Department of Histology and Embryology, Poznan University of Medical Sciences, Poland.
authors.forename: Michał
authors.initials: M
authors.lastname: Nowicki
mesh_terms: D002648:Child; D002675:Child, Preschool; D004351:Drug Resistance / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D019746:Intramolecular Oxidoreductases / Q000235:genetics*; D008263:Macrophage Migration-Inhibitory Factors / Q000235:genetics*; D008297:Male; D009404:Nephrotic Syndrome / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D020641:Polymorphism, Single Nucleotide; D013256:Steroids / Q000008:administration & dosage*
chemical_list: D008263:Macrophage Migration-Inhibitory Factors; D013256:Steroids; D019746:Intramolecular Oxidoreductases; C515598:MIF protein, human