Franks S, White D, Gilling-Smith C, Carey A, Waterworth D, Williamson R
Department of Obstetrics & Gynaecology, St. Mary's Hospital Medical School, Imperial College, London, UK.
Baillieres Clin Endocrinol Metab. 1996 Apr;10(2):193-203. doi: 10.1016/s0950-351x(96)80057-7.
A single base change has been found in the promoter region of CYP17, the gene encoding P450c17 alpha, which appears to be a significant factor in the expression of hyperandrogenism in PCO but which can be excluded as the primary genetic defect. These findings are consistent with the biochemical data from the studies of patients with PCOS reported above, in which the production of ovarian 17 hydroxyprogesterone and androstenedione were observed to be greatly increased but the generation of progesterone was also exaggerated in PCO theca. Thus, genetic factors may well be involved in the observed dysregulation of 17 hydroxylase/17,20 lyase, but this does not appear to be the whole story. It remains a tenable hypothesis that a single-gene effect is the major cause of PCOS and that a gene involved in the expression of androgen production will be implicated. On the other hand, increased androgen production may be a reflection of an 'upstream' abnormality in the ovary, perhaps involving the fundamental processes of proliferation, differentiation and atresia in ovarian follicles. It is also possible that PCOS is truly polygenic and that CYP17 is one of several genes-including those related to insulin secretion and action-that contribute to the PCOS phenotype. Further candidate genes will need to be investigated using well-characterized, large families, but if several predisposing genes are involved, other approaches may be applicable, for example analysis of shared alleles by affected sibling pairs, which has proved valuable in understanding the genetics of type 1 diabetes (Davies et al, 1994). In conclusion, PCOS--one of the most common endocrinopathies--remains an enigmatic condition but one which may prove to be an important model for understanding the interaction of genetic and environmental factors in the aetiology of endocrine disorders.
在编码P450c17α的CYP17基因的启动子区域发现了一个单碱基变化，这似乎是多囊卵巢综合征（PCO）中高雄激素血症表达的一个重要因素，但可排除其作为主要遗传缺陷。这些发现与上述PCOS患者研究中的生化数据一致，在该研究中观察到PCO卵泡膜细胞中卵巢17羟孕酮和雄烯二酮的产生大幅增加，但孕酮的生成也被夸大。因此，遗传因素很可能参与了观察到的17羟化酶/17,20裂解酶的失调，但这似乎并不是全部情况。单基因效应是PCOS的主要原因且涉及雄激素产生表达的基因这一假说仍然成立。另一方面，雄激素产生增加可能反映了卵巢中的“上游”异常，可能涉及卵泡增殖、分化和闭锁的基本过程。也有可能PCOS是真正的多基因疾病，而CYP17是包括与胰岛素分泌和作用相关基因在内的几个导致PCOS表型的基因之一。需要使用特征明确的大家庭来研究更多候选基因，但如果涉及多个易感基因，可能适用其他方法，例如通过患病同胞对分析共享等位基因，这已被证明在理解1型糖尿病的遗传学方面很有价值（戴维斯等人，1994年）。总之，PCOS作为最常见的内分泌疾病之一，仍然是一种神秘的病症，但可能被证明是理解内分泌疾病病因中遗传和环境因素相互作用的重要模型。
