POLYCYSTIC OVARIES AND PREMATURE MALE PATTERN BALDNESS ARE ASSOCIATED WITH ONE ALLELE OF THE STEROID-METABOLISM GENE CYP17
POLYCYSTIC OVARIES AND PREMATURE MALE PATTERN BALDNESS ARE ASSOCIATED WITH ONE ALLELE OF THE STEROID-METABOLISM GENE CYP17
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DOI：
10.1093/hmg/3.10.1873
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发表时间：
1994-10-01
影响因子：
3.5
通讯作者：
WILLIAMSON, R
中科院分区：
文献类型：
--
作者：
CAREY, AH;WATERWORTH, D;WILLIAMSON, R
已对 14 个白人家庭的 81 名受影响个体进行了评估，其中多囊卵巢/男性型秃发 (PCO/MPB) 作为常染色体显性表型分离 (1)。染色体 10q24.3 上编码 P450c17 α（17 α 羟化酶；17/20 裂解酶）的基因 CYP17 是雄激素生物合成的限速步骤。我们通过异源双链分析鉴定了 CYP17 5' 启动子区域中的一个新的单碱基变化。这会创建一个额外的 SP1 型（CCACC 盒）启动子位点，可能会导致表达增加。这种碱基变化还为限制性酶 MspA1 创建了一个识别位点，从而允许简单的筛选过程。与连续匹配的对照 (P = 0.03) 相比，这一碱基变化 (A2) 的存在与连续识别的患有 PCO 的白人女性的受影响状态之间存在显着关联，其中至少具有一个 A2 等位基因的女性的比值比为 3.57，或者与比值比为 2.50 的随机人群 (P = 0.02) 相比。在这 14 个家庭中，与正常亲属相比，患有 PCO 或 MPB 的成员与至少一种 A2 等位基因的发生显着相关，优势比为 2.20 (P = 0.05)。碱基变化并不与显示关联的家族内受影响的表型共分离，这表明 CYP17 的这种突变不会导致 PCO/MPB。 CYP17 基因 A2 等位基因的变异是改变 PCO/MPB 家族表达的重要因素，在该家族中 PCO/MPB 已被证明是作为单基因疾病分离的，但它被排除为主要遗传缺陷。
Fourteen Caucasian families with 81 affected individuals have been assessed in which polycystic ovaries/male pattern baldness (PCO/MPB) segregates as an autosomal dominant phenotype (1). The gene CYP17, coding for P450c17 alpha (17 alpha-hydroxylase; 17/20 lyase) on chromosome 10q24.3 is the rate-limiting step in androgen biosynthesis. We have identified a new single base change in the 5' promoter region of CYP17 by heteroduplex analysis. This creates an additional SP1-type (CCACC box) promoter site, which may cause increased expression. This base change also creates a recognition site for the restriction enzyme MspA1 allowing a simple screening procedure. There is a significant association between the presence of this base change (A2) and the affected state for consecutively identified Caucasian women with PCO as compared either to consecutively matched controls (P = 0.03) with an odds ratio for those with at least one A2 allele of 3.57, or to a random population (P = 0.02) with an odds ratio of 2.50. Within the fourteen families, members with PCO or MPB have a significant association with the occurrence of at least one A2 allele compared to their normal relatives, with an odds ratio of 2.20 (P = 0.05). The base change does not cosegregate with the affected phenotype within the families showing association, demonstrating that this mutation of CYP17 does not cause PCO/MPB. Variation in the A2 allele of the CYP17 gene is a significant factor modifying the expression of PCO/MPB in families where it has been demonstrated to segregate as a single gene disorder, but it is excluded as the primary genetic defect.