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Response to prednisone in relation to NR3C1 intron B polymorphisms in childhood nephrotic syndrome

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Abstract

The variation in time required to obtain cessation of proteinuria in children with nephrotic syndrome (NS) represents one aspect of the variations shown by these children in response to glucocorticoid (GC) treatment. Polymorphism of the GC receptor gene (NR3C1) has been postulated as one factor that would partially explain differences in both the clinical presentation and the reaction to treatment in GC-treated diseases. We genotyped 118 children diagnosed with NS who initially responded to oral GC treatment [steroid-responsive nephrotic syndrome (SRNS) group] and 136 healthy children for three intron B single nucleotide polymorphisms of NR3C1, namely Bcl I (C/G), rs33389 (C/T) and rs33388 (A/T). In the SRNS group, we performed a three-marker haplotype analysis of NR3C1 in relation to the response to prednisone, represented as time to proteinuria resolution (TPR) as categorical and ordinal variable. Results: The distribution of individual polymorphisms and three-marker haplotypes was similar in healthy children and SRNS patients (all p values >0.05). The GTA haplotype was associated with a higher GC sensitivity, as determined by TPR, and was found to be more prevalent in early (response ≤7 days) than late (response >7 days) prednisone responders (27.7 vs. 14.5%, hap-score = −2.22, p = 0.05 adjusted for biopsy results). These results are in agreement with those reported earlier on an association of intron B haplotypes with GC sensitivity. The distribution of GC polymorphisms among the residents of north-eastern Poland was also determined.

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References

  1. Hogg RJ, Portman RJ, Milliner D, Lemley KV, Eddy A, Ingelfinger J (2000) Evaluation and management of proteinuria and nephrotic syndrome in children: recommendations from a pediatric nephrology panel established at the National Kidney Foundation conference on proteinuria, albuminuria, risk, assessment, detection, and elimination (PARADE). Pediatrics 105:1242–1249

    Article  CAS  Google Scholar 

  2. Lu NZ, Cidlowski JA (2006) Glucocorticoid receptor isoforms generate transcription specificity. Trends Cell Biol 16:301–307

    Article  CAS  Google Scholar 

  3. Carlotti AP, Franco PB, Elias LL, Facincani I, Costa EL, Foss N, Moreira AC, de Castro M (2004) Glucocorticoid receptors, in vitro steroid sensitivity, and cytokine secretion in idiopathic nephrotic syndrome. Kidney Int 65:403–408

    Article  Google Scholar 

  4. Fujii Y, Khoshnoodi J, Takenaka H, Hosoyamada M, Nakajo A, Bessho F, Kudo A, Takahashi S, Arimura Y, Yamada A, Nagasawa T, Ruotsalainen V, Tryggvason K, Lee AS, Yan K (2006) The effect of dexamethasone on defective nephrin transport caused by ER stress: a potential mechanism for the therapeutic action of glucocorticoids in the acquired glomerular diseases. Kidney Int 69:1350–1359

    Article  CAS  Google Scholar 

  5. Constantinescu AR, Shah HB, Foote EF, Weiss LS (2000) Predicting first-year relapses in children with nephrotic syndrome. Pediatrics 105:492–495

    Article  CAS  Google Scholar 

  6. Bray PJ, Cotton RG (2003) Variations of the human glucocorticoid receptor gene (NR3C1): pathological and in vitro mutations and polymorphisms. Hum Mutat 21:557–568

    Article  CAS  Google Scholar 

  7. Kino T, De Martino MU, Charmandari E, Mirani M, Chrousos GP (2003) Tissue glucocorticoid resistance/hypersensitivity syndromes. J Steroid Biochem Mol Biol 85:457–467

    Article  CAS  Google Scholar 

  8. Stevens A, Ray DW, Zeggini E, John S, Richards HL, Griffiths CE, Donn R (2004) Glucocorticoid sensitivity is determined by a specific glucocorticoid receptor haplotype. J Clin Endocrinol Metab 89:892–897

    Article  CAS  Google Scholar 

  9. Report of the International Study of Kidney Disease in Children (1982) Early identification of frequent relapsers among children with minimal change nephrotic syndrome. A report of the International Study of Kidney Disease in Children. J Pediatr 101:514–518

    Article  Google Scholar 

  10. Fleury I, Beaulieu P, Primeau M, Labuda D, Sinnett D, Krajinovic M (2003) Characterization of the BclI polymorphism in the glucocorticoid receptor gene. Clin Chem 49:1528–1531

    Article  CAS  Google Scholar 

  11. Zou GY, Donner A (2006) The merits of testing Hardy-Weinberg equilibrium in the analysis of unmatched case-control data: a cautionary note. Ann Hum Genet 70:923–933

    Article  CAS  Google Scholar 

  12. Schaid DJ, Rowland CM, Tines DE, Jacobson RM, Poland GA (2002) Score tests for association between traits and haplotypes when linkage phase is ambiguous. Am J Hum Genet 70:425–434

    Article  Google Scholar 

  13. Turner JD, Schote AB, Macedo JA, Pelascini LP, Muller CP (2006) Tissue specific glucocorticoid receptor expression, a role for alternative first exon usage? Biochem Pharmacol 72:1529–1537

    Article  CAS  Google Scholar 

  14. Russcher H, Dalm VA, de Jong FH, Brinkmann AO, Hofland LJ, Lamberts SW, Koper JW (2007) Associations between promoter usage and alternative splicing of the glucocorticoid receptor gene. J Mol Endocrinol 38:91–98

    Article  CAS  Google Scholar 

  15. Cartegni L, Chew SL, Krainer AR (2002) Listening to silence and understanding nonsense: exonic mutations that affect splicing. Nat Rev Genet 3:285–298

    Article  CAS  Google Scholar 

  16. Rajeevan MS, Smith AK, Dimulescu I, Unger ER, Vernon SD, Heim C, Reeves WC (2007) Glucocorticoid receptor polymorphisms and haplotypes associated with chronic fatigue syndrome. Genes Brain Behav 6:167–176

    Article  CAS  Google Scholar 

  17. Donn R, Payne D, Ray D (2007) Glucocorticoid receptor gene polymorphisms and susceptibility to rheumatoid arthritis. Clin Endocrinol 67:342–345

    Article  CAS  Google Scholar 

  18. DeRijk RH, Schaaf M, de Kloet ER (2002) Glucocorticoid receptor variants: clinical implications. J Steroid Biochem Mol Biol 81:103–122

    Article  CAS  Google Scholar 

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Correspondence to Anna Wasilewska.

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Zalewski, G., Wasilewska, A., Zoch-Zwierz, W. et al. Response to prednisone in relation to NR3C1 intron B polymorphisms in childhood nephrotic syndrome. Pediatr Nephrol 23, 1073–1078 (2008). https://doi.org/10.1007/s00467-008-0772-7

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  • DOI: https://doi.org/10.1007/s00467-008-0772-7

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