Journal Article

The clinical course of steroid-sensitive childhood nephrotic syndrome is associated with a functional IL12B promoter polymorphism

Jan Müller-Berghaus, Markus J. Kemper, Bernd Hoppe, Uwe Querfeld, Dirk E. Müller-Wiefel, Grant Morahan, Dirk Schadendorf and Klaus Tenbrock

in Nephrology Dialysis Transplantation

Published on behalf of European Renal Association - European Dialysis and Transplant Assoc

Volume 23, issue 12, pages 3841-3844
Published in print December 2008 | ISSN: 0931-0509
Published online July 2008 | e-ISSN: 1460-2385 | DOI: http://dx.doi.org/10.1093/ndt/gfn395
The clinical course of steroid-sensitive childhood nephrotic syndrome is associated with a functional IL12B promoter polymorphism

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Background. Steroid-sensitive nephrotic syndrome (NS) of childhood is the most common glomerular disease in children. The type and duration of response to corticosteroid therapy are used for clinical classification, and especially patients with steroid dependence often have a complicated course, requiring intensified immunosuppressive treatment. Its cause is still unknown although a cytokine-mediated course of disease has been implicated. Interleukin 12 (IL-12) is critical in determining the type of immune response. The ability of dendritic cells to secrete bioactive IL-12 is associated with a bi-allelic polymorphism within the promoter region of IL12B, the gene encoding the IL-12 p40 subunit. We hypothesized that this genotype may be involved in steroid-sensitive INS.

Methods. Using allele-specific PCR, 79 children with relapsing NS were genotyped for the IL12Bpro polymorphism, and genotype was correlated with clinical phenotype (presence/absence of steroid dependence).

Results. Children with the steroid-dependent course are at a significantly higher frequency homozygous for one IL12B allele compared to children without steroid dependence (46.7% and 17.6%, respectively). This genotype has previously been shown to be associated with impaired IL-12 secretion.

Conclusion. Polymorphisms in the IL12B promoter region associate with two different clinical courses of NS. The IL12Bpro polymorphism may therefore define molecular subgroups with different prognosis. Further studies are needed to evaluate the prognostic value.

Keywords: child; interleukin 12; nephrotic syndrome; Th1; Th2

Journal Article.  2011 words. 

Subjects: Nephrology

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