Response to prednisone in relation to NR3C1 intron B polymorphisms in childhood nephrotic syndrome.
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 <or=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.
Zalewski
Grzegorz
G
Department of Clinical Molecular Biology, Medical University of Białystok, Białystok, Poland.
Wasilewska
Anna
A
Zoch-Zwierz
Walentyna
W
Chyczewski
Lech
L
D000284:Administration, Oral; D002648:Child; D002675:Child, Preschool; D005260:Female; D005787:Gene Frequency; D005938:Glucocorticoids / Q000008:administration & dosage / Q000627:therapeutic use*; D006239:Haplotypes; D006801:Humans; D007438:Introns; D008297:Male; D009404:Nephrotic Syndrome / Q000150:complications / Q000188:drug therapy* / Q000235:genetics; D010641:Phenotype; D011044:Poland; D020641:Polymorphism, Single Nucleotide; D011239:Prednisolone / Q000008:administration & dosage / Q000627:therapeutic use*; D011507:Proteinuria / Q000188:drug therapy* / Q000235:genetics; D011965:Receptors, Glucocorticoid / Q000235:genetics*; D012189:Retrospective Studies; D013997:Time Factors; D016896:Treatment Outcome
D005938:Glucocorticoids; C497713:NR3C1 protein, human; D011965:Receptors, Glucocorticoid; D011239:Prednisolone