Association of the steroid synthesis gene CYP11a with polycystic ovary syndrome and hyperandrogenism
Association of the steroid synthesis gene CYP11a with polycystic ovary syndrome and hyperandrogenism
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DOI：
10.1093/hmg/6.3.397
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发表时间：
1997-03-01
影响因子：
3.5
通讯作者：
Williamson, R
中科院分区：
文献类型：
--
作者：
Gharani, N;Waterworth, DM;Williamson, R
多囊卵巢综合征（PCOS）的病因学与雄激素的生物合成和/或代谢紊乱有关。我们检测了20个多囊卵巢综合征家系中雄激素合成和代谢的两个关键酶--胆固醇侧链裂解酶（CYP 11 a）和芳香化酶（CYP 19）的基因分离，所有分析均排除了CYP 19与PCOS的共分离。表明该位点不是该综合征风险的主要决定因素，然而，我们的结果提供了与CYP 11 a位点连锁的证据（NPL评分= 3.03，p = 0.003），使用显性模型的参数分析表明遗传异质性，产生的最大HLOD评分为2.7（α = 0.63），一项对97例连续鉴定的欧脂蛋白与PCOS和匹配对照的关联研究表明，CYP 11 a 5' UTR五核苷酸重复多态性与多毛PCOS受试者有显著的等位基因关联CYP 11 A基因多态性与多囊卵巢综合征患者血清总睾酮水平之间也存在显著的相关性（p = 0.002）。我们的数据表明，CYP 11 a基因多态性在高雄激素血症的病因学中可能起重要作用，高雄激素血症是多囊卵巢综合征的常见特征。
Biochemical data implicate an underlying disorder of androgen biosynthesis and/or metabolism in the aetiology of polycystic ovary syndrome (PCOS), We have examined the segregation of the genes coding for two key enzymes in the synthesis and metabolism of androgens, cholesterol side chain cleavage (CYP11a) and aromatase (CYP19), with PCOS in 20 multiply-affected families, All analyses excluded CYP19 co-segregation with PCOS, demonstrating that this locus is not a major determinant of risk for the syndrome, However, our results provide evidence for linkage to the CYP11a locus (NPL score = 3.03, p = 0.003), Parametric analysis using a dominant model suggests genetic heterogeneity, generating a maximum HLOD score of 2.7 (alpha = 0.63), An association study of 97 consecutively identified Europids with PCOS and matched controls demonstrates significant allelic association of a CYP11a 5' UTR pentanucleotide repeat polymorphism with hirsute PCOS subjects (p = 0.03), A strong association was also found between alleles of this polymorphism and total serum testosterone levels in both affected and unaffected individuals (p = 0.002), Our data demonstrate that variation in CYP11a may play an important role in the aetiology of hyperandrogenaemia which is a common characteristic of polycystic ovary syndrome.