Adrenal 21-hydroxylase gene mutations in Slovenian hyperandrogenic women: evaluation of corticotrophin stimulation and HLA polymorphisms in screening for carrier status
| Autor: | K Breskvar, J Prezelj, Vita Dolzan, B Vidan-Jeras |
|---|---|
| Rok vydání: | 1999 |
| Předmět: |
Adult
Heterozygote medicine.medical_specialty Adolescent Hydrocortisone medicine.drug_class Endocrinology Diabetes and Metabolism Slovenia Population Stimulation Human leukocyte antigen Biology Gene mutation White People Basal (phylogenetics) Exon Endocrinology HLA Antigens Internal medicine Adrenal Glands medicine Humans education DNA Primers education.field_of_study Polymorphism Genetic 17-alpha-Hydroxyprogesterone 21-Hydroxylase General Medicine Androgen Case-Control Studies Mutation biology.protein Female Steroid 21-Hydroxylase Hyperandrogenism |
| Zdroj: | European Journal of Endocrinology. :132-139 |
| ISSN: | 1479-683X 0804-4643 |
| DOI: | 10.1530/eje.0.1410132 |
| Popis: | 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. DESIGN: Molecular analysis of CYP21 gene, ACTH stimulation and human leucocyte antigen (HLA) typing were performed in 83 consecutive Slovenian hyperandrogenic women. MEASUREMENTS: 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. |
| Databáze: | OpenAIRE |
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