Dolzan V, Prezelj J, Vidan-Jeras B, Breskvar K
Institute of Biochemistry, Faculty of Medicine, Ljubljana, Slovenia.
Eur J Endocrinol. 1999 Aug;141(2):132-9. doi: 10.1530/eje.0.1410132.
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.
Molecular analysis of CYP21 gene, ACTH stimulation and human leucocyte antigen (HLA) typing were performed in 83 consecutive Slovenian hyperandrogenic women.
Cortisol and 17-OHP concentrations were measured at baseline and 60 min after ACTH stimulation. Basal adrenal androgen concentrations were also measured.
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.
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.
在基因水平上研究斯洛文尼亚高雄激素女性中21-羟化酶缺乏症的发病率。以往的内分泌学研究表明，高雄激素女性中21-羟化酶缺乏症的发病率存在很大差异。重新评估了促肾上腺皮质激素（ACTH）刺激后17-羟孕酮（17-OHP）反应及人类白细胞抗原（HLA）分型在筛查携带者状态方面的预测价值。
对83例连续的斯洛文尼亚高雄激素女性进行CYP21基因的分子分析、ACTH刺激试验及人类白细胞抗原（HLA）分型。
在基线及ACTH刺激后60分钟测量皮质醇和17-OHP浓度。同时测量基础肾上腺雄激素浓度。
83例高雄激素患者中无一例患有非经典型21-羟化酶缺乏症，但81例患者中有12例（14.8%）在刺激后17-OHP浓度升高，提示为携带者状态。12例患者中只有3例（25%）17-OHP浓度升高可归因于CYP21基因突变携带者状态，而69例刺激后17-OHP浓度正常的患者中有7例（10.1%）被发现为CYP21基因突变携带者，这表明ACTH刺激作为21-羟化酶缺乏症携带者筛查试验的阳性预测值较低。83例患者中共鉴定出11例携带者：发现7例CYP21基因缺失/转换、2例Gln(318)Stop和1例Val(281)Leu突变以及1例从外显子4延伸至外显子7的基因转换。在该斯洛文尼亚人群中证实了Val(281)Leu突变与HLA-B14抗原之间的关联。
在斯洛文尼亚高雄激素患者中，基础或ACTH刺激后的17-OHP浓度并非21-羟化酶缺乏症携带者状态的良好指标。只有通过CYP21基因的分子分析才能可靠地筛查21-羟化酶缺乏症的携带者。
