title: Adrenal 21-hydroxylase gene mutations in Slovenian hyperandrogenic women: evaluation of corticotrophin stimulation and HLA polymorphisms in screening for carrier status.
abstract: OBJECTIVE
  To study the incidence of 21-hydroxylase deficiency in Slovenian hyperandrogenic women, at the gene level. Previous endocrine studies indicated large differences in the incidence of 21-hydroxylase deficiency in hyperandrogenic women. The predictive values of the 17-hydroxyprogesterone (17-OHP) response to ACTH stimulation and of HLA typing in screening for carrier status were re-evaluated.
  
  
  METHODS
  Molecular analysis of CYP21 gene, ACTH stimulation and human leucocyte antigen (HLA) typing were performed in 83 consecutive Slovenian hyperandrogenic women.
  
  
  METHODS
  Cortisol and 17-OHP concentrations were measured at baseline and 60 min after ACTH stimulation. Basal adrenal androgen concentrations were also measured.
  
  
  RESULTS
  None of 83 hyperandrogenic patients was affected with non-classical 21-hydroxylase deficiency, but 12 of 81 patients (14.8%) had high concentrations of 17-OHP after stimulation, indicative of carrier status. The increase in 17-OHP concentrations could be explained by a carrier status for CYP21 gene mutations in only three of 12 patients (25%), whereas seven of 69 patients (10. 1%) with normal concentrations of 17-OHP after stimulation were found to be carriers of CYP21 gene mutations, indicating low positive predictive values of ACTH stimulation as a screening test for carriers of 21-hydroxylase deficiency. In total, 11 carriers were identified among 83 patients: seven CYP21 gene deletions/conversions, two Gln(318)Stop and one Val(281)Leu mutation and one gene conversion extending from exon 4 to exon 7 were found. The association between Val(281)Leu mutation and HLA-B14 antigen was confirmed in this Slovenian population.
  
  
  CONCLUSIONS
  Basal or ACTH-stimulated 17-OHP concentrations are not a good indicator of the carrier status for 21-hydroxylase deficiency among Slovenian hyperandrogenic patients. Reliable screening for carriers of 21-hydroxylase deficiency is possible only by molecular analysis of the CYP21 gene.
authors.affiliation: Institute of Biochemistry, Faculty of Medicine, Ljubljana, Slovenia. dolzan@ibmi.mf.uni-lj.si
authors.forename: V
authors.initials: V
authors.lastname: Dolzan
authors.forename: J
authors.initials: J
authors.lastname: Prezelj
authors.forename: B
authors.initials: B
authors.lastname: Vidan-Jeras
authors.forename: K
authors.initials: K
authors.lastname: Breskvar
mesh_terms: D019326:17-alpha-Hydroxyprogesterone / Q000097:blood; D000293:Adolescent; D000311:Adrenal Glands / Q000201:enzymology*; D000328:Adult; D016022:Case-Control Studies; D017931:DNA Primers; D005260:Female; D006680:HLA Antigens / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D017588:Hyperandrogenism / Q000097:blood / Q000235:genetics*; D009154:Mutation; D011110:Polymorphism, Genetic; D017524:Slovenia; D013255:Steroid 21-Hydroxylase / Q000235:genetics*; D044465:White People / Q000235:genetics*
chemical_list: D017931:DNA Primers; D006680:HLA Antigens; D019326:17-alpha-Hydroxyprogesterone; D013255:Steroid 21-Hydroxylase; D006854:Hydrocortisone