中国汉族雄激素过多症女性21-羟化酶缺陷症携带者基因检测

目的　初步了解中国汉族女性雄激素过多症患者中2 1-羟化酶缺陷症(2 1- hydroxylasedeficiency,2 1- OHD)携带者发生率,探讨促肾上腺皮质激素(adrenocorticotropic hormone,ACTH)兴奋试验结果与基因突变检测结果的相关性。方法　82例汉族女性雄激素过多症患者及14名健康女性进行ACTH兴奋试验,并应用PCR扩增产生限制性酶切位点方法检测已知的9个2 1- OHD常见突变位点。结果　雄激素过多组(n=82 ) F0 显著高于正常对照组(P<0 .0 1) ;17- OHP0 及17- OHP6 0 也显著高于对照组(P<0 .0 1) ,而F6 0 差异没有统计学意义(P>0 .0 5 )。比较17- OHP净增值及17- OHP净增值/ F净增值,雄激素过多组也均显著高于正常对照组(P<0 .0 1)。正常对照组未检测出细胞色素P4 5 0 (cytochrome P4 5 02 1,CYP2 1)基因突变。发现雄激素过多组4例CYP2 1基因突变携带者(4/ 82 ,4 .9% ) ,分别携带V2 81L(2例) ,i2 g及Q318X(各1例) ,携带者的ACTH兴奋试验结果与正常对照及未检出突变的雄激素过多症患者的结果存在一定的交叉。结论　82例汉族雄激素过多症女性中2 1- OHD携带者为4例,占4 .9%。ACTH兴奋试验不能用以发现携带者,应进行基因检测确定。

Screening 21-hydroxylase deficiency carriers in androgen excess women of Chinese Han nationality

Objective To gain a primary understanding of the prevalence of 21-hydroxylase deficiency(21-OHD) heterozygote (carrier) among androgen excess women of Chinese Han nationality, compare the molecular genetic changes therein revealed with the results of adrenocorticotropic hormone (ACTH) stimulating test, and assess the carriers' phenotype-genotype correlation. Methods Eighty-two androgen excess cases and 14 healthy women underwent ACTH stimulating test during the follicular phase. Molecular genetic analysis of CYP21 for 9 common mutations was performed with the method of amplification-created restriction sites. Results In androgen excess group, the basal level of F 0 ( P <0 01), as well as basal 17-OHP 0 and the ACTH stimulated concentrations of 17-OHP 60 were much higher than controls ( P <0 01), and there was no obvious discrepancy in F 60 ( P >0.05). The net increase of 17-OHP and the ratio of net increase of 17-OHP to net increase of F were also higher than controls ( P <0 01). No CYP21 gene mutations were found in control group. Four patients of the androgen excess group were identified as heterozygous carriers of CYP21 mutations. The ACTH stimulating test results from gene normal patients and from carriers overlapped to a certain extent. Conclusion Among 82 patients of Chinese Han nationality androgen excess women, 4.9% were 21-OHD heterozygous. The response of serum 17-OHP is not useful for predictingCYP21 gene mutation carrier status. Genotyping is the most reliable method to detect carrier.