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Association of the macrophage migration inhibitory factor −173*C allele with childhood nephrotic syndrome

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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.

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Authors and Affiliations

  1. Unità Operativa di Nefrologia e Dialisi, IRCCS Ospedale Pediatrico Bambino Gesù, Rome, Italy

    Marina Vivarelli, Gilda Stringini & Francesco Emma

  2. Laboratorio di Reumatologia, IRCCS Ospedale Pediatrico Bambino Gesù, Rome, Italy

    Leila Emma D’Urbano & Fabrizio De Benedetti

  3. Laboratorio di Fisiopatologia dell’uremia, IRCCS Istituto G. Gaslini, Genova, Italy

    Gian Marco Ghiggeri & Gianluca Caridi

  4. Arthritis Research Campaign’s Epidemiology Unit, University of Manchester, Manchester, UK

    Rachelle Donn

  5. Unità di Epidemiologia, IRCCS Ospedale Pediatrico Bambino Gesù, Rome, Italy

    Alberto Tozzi

  6. Direzione Scientifica IRCCS Ospedale Pediatrico Bambino Gesù, Piazza S. Onofrio 4, 00165, Rome, Italy

    Fabrizio De Benedetti

Authors
  1. Marina Vivarelli
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  2. Leila Emma D’Urbano
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  3. Gilda Stringini
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  4. Gian Marco Ghiggeri
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  5. Gianluca Caridi
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  6. Rachelle Donn
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  7. Alberto Tozzi
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  8. Francesco Emma
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  9. Fabrizio De Benedetti
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Corresponding author

Correspondence to Fabrizio De Benedetti.

Additional information

Marina Vivarelli and Leila Emma D’Urbano contributed equally to the work.

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Vivarelli, M., D’Urbano, L.E., Stringini, G. et al. Association of the macrophage migration inhibitory factor −173*C allele with childhood nephrotic syndrome. Pediatr Nephrol 23, 743–748 (2008). https://doi.org/10.1007/s00467-007-0729-2

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  • DOI: https://doi.org/10.1007/s00467-007-0729-2

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