基因型明确的17 α-羟化酶/17,20-裂解酶缺陷症杂合子肾上腺皮质功能的研究
기인형명학적17 α-간화매/17,20-렬해매결함증잡합자신상선피질공능적연구
Identification of steroid biosynthetic defects in genotype-proven heterozygote individuals with 17α-hydroxylase/17,20-lyase deficiency
  • 万方数据
    中华内分泌代谢杂志 중화내분비대사잡지
    CHINESE JOURNAL OF ENDOCRINOLOGY AND METABOLISM
    2010年 8期 633-638 ,共6页

    乔洁%刘炳丽%梁军%陈霞%左春林%顾燕云%龚静%唐金凤%伍贻新%金燕%陆颖理%吴万龄%宋怀东%陈名道

    교길%류병려%량군%진하%좌춘림%고연운%공정%당금봉%오이신%금연%륙영리%오만령%송부동%진명도

    肾上腺%类固醇%P450c17缺陷%杂合子%CYP17A1基因%基因突变 腎上腺%類固醇%P450c17缺陷%雜閤子%CYP17A1基因%基因突變
    신상선%류고순%P450c17결함%잡합자%CYP17A1기인%기인돌변
    Adrenal glands%Steroid%P450c17 deficiency%Heterozygous%CYP17A1 gene%Mutation
    目的 明确携带CYP17A1基因突变的杂合子个体肾上腺类固醇激素合成功能.方法 对17α-羟化酶和17,20-裂解酶缺陷(17OHD)5个家系的8例患者和14例家系成员,通过PCR产物直接测序的方法来鉴定CYP17A1基因突变,并测定CYP17A1基因突变携带者与45名年龄、性别匹配的正常个体在ACTH兴奋前后肾上腺皮质激素的变化.结果 发现5个家系14例CYP17A1基因突变的携带者中,7例为D487_F489del,6例为Y329fs,1例为H373L.杂合携带者基础和ACTH刺激后的皮质醇水平均低于正常对照,而兴奋后的皮质酮水平高于正常.杂合子的皮质酮与皮质醇的比值在ACTH兴奋前后皆高于正常对照.而男性杂合子在ACTH兴奋前后孕酮水平以及孕酮与17-羟孕酮比值也均都高于正常对照.D487_F489del和Y329fs两组杂合子之间的激素水平无显著差异.结论 与CYP21A2基因突变的携带者体内的21-羟化酶活性轻度受损相类似,CYP17A1基因突变杂合携带者的肾上腺类固醇激素合成已有异常.
    목적 명학휴대CYP17A1기인돌변적잡합자개체신상선류고순격소합성공능.방법 대17α-간화매화17,20-렬해매결함(17OHD)5개가계적8례환자화14례가계성원,통과PCR산물직접측서적방법래감정CYP17A1기인돌변,병측정CYP17A1기인돌변휴대자여45명년령、성별필배적정상개체재ACTH흥강전후신상선피질격소적변화.결과 발현5개가계14례CYP17A1기인돌변적휴대자중,7례위D487_F489del,6례위Y329fs,1례위H373L.잡합휴대자기출화ACTH자격후적피질순수평균저우정상대조,이흥강후적피질동수평고우정상.잡합자적피질동여피질순적비치재ACTH흥강전후개고우정상대조.이남성잡합자재ACTH흥강전후잉동수평이급잉동여17-간잉동비치야균도고우정상대조.D487_F489del화Y329fs량조잡합자지간적격소수평무현저차이.결론 여CYP21A2기인돌변적휴대자체내적21-간화매활성경도수손상유사,CYP17A1기인돌변잡합휴대자적신상선류고순격소합성이유이상.
    Objective To investigate the adrenal steroidogenic function in genotype-proven heterozygotes carrying mutations in CYP17A1 gene in vivo. Methods Eight patients and 14 family members from 5 families with 17-hydroxylase/17,20-lyase deficiency (17OHD) were recruited. The mutations of the CYP17A1 gene in these individuals were screened by direct sequencing of PCR products. The hormonal response to ACTH was evaluated in the 14 genotype-proven carriers and 45 age- and sex-matched normal subjects. Results Three mutations were found in 5 unrelated families. 14 carriers with CYP17A1 mutation were identified, including 7 heterozygotes with D487_F489del, 6 with Y329fs, and 1 for H373L. Compared to the normal subjects, the carriers exhibited lower basal and ACTH-stimulated cortisol levels, but higher ACTH-stimulated corticosterone level. The ratios of corticosterone to cortisol in the genotype-proven heterozygotes were higher than those of normal individuals at baseline and following ACTH-stimulation. Similarly, progesterone level and ratios of progesterone to 17-hydroxyprogesterone in the male heterozygotes were also higher than that of normal individuals before and after stimulation. No significant differences were observed in the hormone levels between two genotypes (D487_F489del vs Y329fs). Conclusions Genotype-proven carriers of 17OHD without apparent clinical symptoms exhibit decreased enzyme activity,analogous to mildly impaired adrenal 21-hydroxylase activity in the carriers of CYP21 A2 gene mutation.
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