GLCCI1 single nucleotide polymorphisms in pediatric nephrotic syndrome.
BACKGROUND
Empiric steroid therapy is the first-line therapy for pediatric nephrotic syndrome, but treatment response is variable. There are few predictors of steroid-responsiveness, although evidence for genetic factors does exist. Single nucleotide polymorphisms (SNPs) have been recently identified in the promoter region of glucocorticoid-induced transcript 1 gene (GLCCI1) which affect steroid-responsiveness in asthmatic patients. Independently, GLCCI1 was identified as a podocyte protein, the loss of which disrupts the function of the glomerular filtration barrier. We therefore examined whether SNPs associated with the steroid-responsive expression of GLCCI1 might predict steroid-responsiveness in nephrotic syndrome.


METHODS
A cohort of 211 pediatric patients with nephrotic syndrome and 102 controls were genotyped; among the cases, 117 were initial steroid responders, while 94 did not respond to oral steroids. No statistically significant differences were noted among the groups, although there was a trend based on the comparison of the small subgroups of steroid-responsive and non-responsive patients with biopsy-proven minimal change disease.


CONCLUSIONS
While larger cohorts are needed to ascertain the possibility of a small effect of GLCCI1 SNPs on the steroid-responsiveness of nephrotic syndrome, the GLCCI1 SNPs associated with steroid-responsiveness in asthmatic patients are unlikely to have a clinically actionable impact in pediatric nephrotic syndrome.
Department of Pediatrics, Seoul National University Children's Hospital, Seoul, Korea.
Hae Il
HI
Cheong
Hee Gyung
HG
Kang
Johannes
J
Schlondorff
D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D004351:Drug Resistance / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D005938:Glucocorticoids / Q000627:therapeutic use*; D006801:Humans; D007223:Infant; D008297:Male; D009404:Nephrotic Syndrome / Q000188:drug therapy* / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011965:Receptors, Glucocorticoid / Q000235:genetics*
C561807:GLCCI1 protein, human; D005938:Glucocorticoids; D011965:Receptors, Glucocorticoid