NDT Advance Access published online on July 15, 2008
Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfn395
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The clinical course of steroid-sensitive childhood nephrotic syndrome is associated with a functional IL12B promoter polymorphism
1 Skin Cancer Unit, German Cancer Research Centre, Heidelberg 2 Paul-Ehrlich-Institut, Langen 3 Department of Paediatric Nephrology, University Children's Hospital, Hamburg 4 Department of Paediatric Nephrology, University Children's Hospital of Cologne 5 Department of Paediatric Nephrology, Charite University Hospital, Berlin, Germany 6 School of Medicine and Dentistry, University of Western Australia, Perth, Australia 7 Department of Paediatrics, University of Aachen, Germany
Correspondence and offprint requests to: Klaus Tenbrock, University Hospital, Department of Paediatrics, University of Aachen, Pauwelsstr, 3052074 Aachen, Germany. Tel: +49-241-8088-785; Fax: +49-241-8088-2599; E-mail: ktenbrock{at}ukaachen.de
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Abstract |
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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
Received for publication: 11.10.07
Accepted in revised form: 20. 6.08