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Genetic and in vivo determinants of glucocorticoid sensitivity in relation to clinical outcome of childhood nephrotic syndrome
- Source :
- Kidney International, 85(6), 1444-1453. ELSEVIER SCIENCE INC, Pediatric Nephrology, 28(8), 1596-1596. Springer, Teeninga, N, van Holthe, J E, van den Akker, E L T, Kersten, M C, Boersma, E, Krabbe, H G, Knoers, N V A M, van der Heijden, A J, Koper, J W & Nauta, J 2014, ' Genetic and in vivo determinants of glucocorticoid sensitivity in relation to clinical outcome of childhood nephrotic syndrome ', Kidney International, vol. 85, no. 6, pp. 1444-1453 . https://doi.org/10.1038/ki.2013.531, Kidney International, 85(6), 1444-1453. Nature Publishing Group
- Publication Year :
- 2014
-
Abstract
- Following initial glucocorticoid treatment, the clinical course in children with nephrotic syndrome is highly variable. Intrinsic sensitivity to glucocorticoids might be a determinant of this variability. Functional polymorphisms of the glucocorticoid receptor gene NR3C1 have been associated with either relatively impaired (GR-9β) or increased (BclI) glucocorticoid sensitivity. Here, in a prospective, well-defined cohort of children with nephrotic syndrome, we evaluated both carriage of GR-9β+TthIII-1 and BclI haplotypes in 113 children and a dexamethasone suppression test in 90 children in relation to their clinical outcome over a median follow-up of 4.4 years. Carriers of GR-9β+TthIII-1 had a significantly higher incidence of steroid dependence 13/25 (52%) compared with noncarriers 19/75 (25%) with a hazard ratio adjusted for gender, age, and descent of 3.04 with 95% confidence interval 1.37-6.74. Both first and frequent relapses happened significantly more often in GR-9β+TthIII-1 carriers than in noncarriers. There were no significant differences in therapeutic outcomes between carriers and noncarriers of the BclI haplotype. Results of the dexamethasone test showed no associations with clinical outcome. Thus, the GR-9β+TthIII-1 haplotype of the glucocorticoid receptor gene offers new insights into the clinical course of children with nephrotic syndrome.
- Subjects :
- Oncology
Male
Nephrotic Syndrome
Time Factors
Dexamethasone
Glucocorticoid receptor
Recurrence
Risk Factors
Receptors
Prospective Studies
Age of Onset
Prospective cohort study
Child
Netherlands
Remission Induction
Phenotype
Treatment Outcome
Nephrology
Dexamethasone suppression test
Child, Preschool
Prednisolone
Female
Glucocorticoid
medicine.drug
medicine.medical_specialty
Glucocorticoids/adverse effects
Prednisolone/adverse effects
Glucocorticoid Sensitivity
Receptors, Glucocorticoid
Genetic
Predictive Value of Tests
Internal medicine
medicine
Humans
Glucocorticoid/agonists
Polymorphism
Preschool
Glucocorticoids
Polymorphism, Genetic
business.industry
medicine.disease
Nephrotic Syndrome/diagnosis
Haplotypes
Pharmacogenetics
Immunology
business
Nephrotic syndrome
Receptors, Glucocorticoid/agonists
Subjects
Details
- Language :
- English
- ISSN :
- 00852538 and 0931041X
- Volume :
- 85
- Issue :
- 6
- Database :
- OpenAIRE
- Journal :
- Kidney International
- Accession number :
- edsair.doi.dedup.....b33209c6bfc16a04db5cbc4528e5dc68