title: Potential advantage of N363S glucocorticoid receptor polymorphism in 21-hydroxylase deficiency.
abstract: OBJECTIVE
  Congenital adrenal hyperplasia (CAH) shows a range of severity which is explained in part by the different mutations of the CYP21 gene. To better understand the incomplete concordance between genotype and phenotype in CAH the role of the sensitizing N363S polymorphism of the glucocorticoid receptor (GR) was examined in CAH patients.
  
  
  METHODS
  CAH patients were screened for N363S. Laboratory findings and clinical characteristics of carriers and non-carriers were analyzed retrospectively.
  
  
  METHODS
  The CYP21 gene of 200 CAH patients was analyzed by allele-specific PCR. The GR gene was tested for N363S by PCR followed by restriction fragment length polymorphism. Antropometric data (height, weight), degree of intrauterine virilization, hormone concentrations (17-OH-progesterone, dehydroepiandrosterone (DHEA), aldosterone, testosterone, plasma renin activity), substitution doses and clinical course were analyzed.
  
  
  RESULTS
  The carrier frequency of N363S in CAH patients was equivalent to that of the general Hungarian population (6% vs 7.8%). Interestingly, none of the non-classical CAH (NC-CAH) patients were carriers of the polymorphism. Carrier girls had milder genital virilization than mutation-matched non-carrier controls. There was no significant difference between the carriers and non-carriers in either the substitution doses, the hormonal, or the auxiological parameters.
  
  
  CONCLUSIONS
  The association of sensitizing the GR variant with impaired cortisol production in CAH might be compensatory in mild NC-CAH and may prevent severe intrauterine virilization in classical form. Although the exact role of N363S in extrauterine life should be further investigated, the consideration of certain genetic polymorphisms of CAH patients may lead to better, individualized therapeutic regimes.
authors.affiliation: 2nd Department of Paediatrics, Semmelweis University, Faculty of Medicine, Hungary.
authors.forename: A
authors.initials: A
authors.lastname: Luczay
authors.forename: D
authors.initials: D
authors.lastname: Török
authors.forename: A
authors.initials: A
authors.lastname: Ferenczi
authors.forename: J
authors.initials: J
authors.lastname: Majnik
authors.forename: J
authors.initials: J
authors.lastname: Sólyom
authors.forename: Gy
authors.initials: G
authors.lastname: Fekete
mesh_terms: D000312:Adrenal Hyperplasia, Congenital / Q000175:diagnosis / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006580:Genetic Carrier Screening / Q000379:methods; D005838:Genotype; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011965:Receptors, Glucocorticoid / Q000235:genetics*; D013255:Steroid 21-Hydroxylase / Q000235:genetics*
chemical_list: D011965:Receptors, Glucocorticoid; D013255:Steroid 21-Hydroxylase