title: Association of the macrophage migration inhibitory factor -173*C allele with childhood nephrotic syndrome.
abstract: Macrophage migration inflammatory factor (MIF) is a proinflammatory cytokine with a unique role as the physiologic counterregulator of the immunosuppressive effects of glucocorticoids. MIF has been implicated in the pathogenesis of glomerular inflammation. The MIF promoter contains a G/C polymorphism that is functionally relevant, with the C allele being associated with higher MIF production and linked to susceptibility to inflammatory diseases. We genotyped the MIF -173 polymorphism in 257 children with idiopathic nephrotic syndrome (INS) and 355 controls. Frequency of carriers of the high-producer MIF -173*C allele was higher in patients with INS (31.7%) than in controls (22.0%) [odds ratio (OR) 1.67, p = 0.006] The MIF -173 C allele was more frequent in steroid-resistant patients (43.5%) compared with steroid responders (22.8%) (OR 2.61, p = 0.0005). This difference was particularly evident in focal segmental glomerulosclerosis patients (OR 14.0, p = 0.002). No association with response to cyclosporin A was found. Carriers of the MIF -173*C allele had a significantly higher probability of end-stage renal disease (ESRD) compared with G/G homozygous patients within 5 years from onset (log rank 5.11 p = 0.024). These results underscore the role of MIF in INS disease progression and in the response to glucocorticoid treatment and suggest that screening of MIF genotype at disease onset may identify patients requiring a more aggressive therapeutic approach.
authors.affiliation: Unità Operativa di Nefrologia e Dialisi, IRCCS Ospedale Pediatrico Bambino Gesù, Rome, Italy.
authors.forename: Marina
authors.initials: M
authors.lastname: Vivarelli
authors.forename: Leila Emma
authors.initials: LE
authors.lastname: D'Urbano
authors.forename: Gilda
authors.initials: G
authors.lastname: Stringini
authors.forename: Gian Marco
authors.initials: GM
authors.lastname: Ghiggeri
authors.forename: Gianluca
authors.initials: G
authors.lastname: Caridi
authors.forename: Rachelle
authors.initials: R
authors.lastname: Donn
authors.forename: Alberto
authors.initials: A
authors.lastname: Tozzi
authors.forename: Francesco
authors.initials: F
authors.lastname: Emma
authors.forename: Fabrizio
authors.initials: F
authors.lastname: De Benedetti
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D002648:Child; D002675:Child, Preschool; D002851:Chromatography, High Pressure Liquid; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005938:Glucocorticoids / Q000627:therapeutic use; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007223:Infant; D019746:Intramolecular Oxidoreductases / Q000235:genetics*; D008263:Macrophage Migration-Inhibitory Factors / Q000235:genetics*; D008297:Male; D009404:Nephrotic Syndrome / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D011110:Polymorphism, Genetic; D011379:Prognosis
chemical_list: D005938:Glucocorticoids; D007166:Immunosuppressive Agents; D008263:Macrophage Migration-Inhibitory Factors; D019746:Intramolecular Oxidoreductases; C515598:MIF protein, human