TY - JOUR
T1 - Association of the macrophage migration inhibitory factor -173*C allele with childhood nephrotic syndrome
AU - Vivarelli, Marina
AU - D'Urbano, Leila Emma
AU - Stringini, Gilda
AU - Ghiggeri, Gian Marco
AU - Caridi, Gianluca
AU - Donn, Rachelle
AU - Tozzi, Alberto
AU - Emma, Francesco
AU - De Benedetti, Fabrizio
PY - 2008/5
Y1 - 2008/5
N2 - 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. © IPNA 2007.
AB - 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. © IPNA 2007.
KW - Childhood
KW - Cyclosporin A
KW - End stage renal disease
KW - Glucocorticoid
KW - Idiopathic nephrotic syndrome
KW - Macrophage migration inhibitory factor
U2 - 10.1007/s00467-007-0729-2
DO - 10.1007/s00467-007-0729-2
M3 - Article
VL - 23
SP - 743
EP - 748
JO - Pediatric Nephrology
JF - Pediatric Nephrology
IS - 5
ER -