Goodarzi Mark O, Xu Ning, Azziz Ricardo
Department of Obstetrics/Gynecology and Center for Androgen Related Disorders, Cedars-Sinai Medical Center, 8635 West Third Street, Los Angeles, CA 90048, USA.
J Clin Endocrinol Metab. 2008 Jul;93(7):2909-12. doi: 10.1210/jc.2008-0403. Epub 2008 Apr 29.
Adrenal androgen excess is common in polycystic ovary syndrome (PCOS) and appears to be heritable. CYP3A7 metabolizes dehydroepiandrosterone and its sulfate (DHEAS). A promoter variant, CYP3A71C, which results in persistent expression in adults, was associated with reduced DHEAS levels in a previous study, which led us to consider CYP3A71C as a modulator of adrenal androgen excess in patients with PCOS.
The objective was to replicate the association between CYP3A7*1C and reduced DHEAS levels in PCOS patients and assess its possible role in modulating testosterone levels.
Women with and without PCOS were genotyped for CYP3A7*1C, and this variant was tested for association with DHEAS and total and free testosterone.
Subjects were recruited from the reproductive endocrinology clinic at the University of Alabama at Birmingham; controls were recruited from the surrounding community. Genotyping took place at Cedars-Sinai Medical Center (Los Angeles, CA).
A total of 287 white women with PCOS and 187 controls were studied.
CYP3A7*1C genotype, PCOS risk, and androgen levels were measured.
PCOS subjects who carried the CYP3A7*1C variant had lower levels of serum DHEAS and total testosterone (P = 0.0006 and 0.046, respectively). The variant was not associated with PCOS risk.
This study replicated prior work of the association of CYP3A7*1C and decreased DHEAS in a different population of young PCOS women, providing further genetic evidence that CYP3A7 plays a potential role in modulation of DHEAS levels. Adult expression of CYP3A7 may modify the PCOS phenotype by ameliorating adrenal androgen excess.
肾上腺雄激素过多在多囊卵巢综合征（PCOS）中很常见，且似乎具有遗传性。细胞色素P450 3A7（CYP3A7）可代谢脱氢表雄酮及其硫酸盐（DHEAS）。在之前的一项研究中，一种导致其在成人中持续表达的启动子变异体CYP3A71C与DHEAS水平降低有关，这使我们认为CYP3A71C是PCOS患者肾上腺雄激素过多的调节因子。
在PCOS患者中重复验证CYP3A7*1C与降低的DHEAS水平之间的关联，并评估其在调节睾酮水平方面的可能作用。
对患有和未患有PCOS的女性进行CYP3A7*1C基因分型，并检测该变异体与DHEAS以及总睾酮和游离睾酮之间的关联。
研究对象招募自阿拉巴马大学伯明翰分校生殖内分泌诊所；对照组从周边社区招募。基因分型在雪松西奈医疗中心（加利福尼亚州洛杉矶）进行。
共研究了287名患有PCOS的白人女性和187名对照者。
检测CYP3A7*1C基因型、PCOS风险和雄激素水平。
携带CYP3A7*1C变异体的PCOS受试者血清DHEAS和总睾酮水平较低（分别为P = 0.0006和0.046）。该变异体与PCOS风险无关。
本研究在另一组年轻PCOS女性人群中重复了之前关于CYP3A7*1C与DHEAS降低之间关联的研究结果，提供了进一步的遗传学证据，表明CYP3A7在调节DHEAS水平中发挥潜在作用。CYP3A7在成人中的表达可能通过改善肾上腺雄激素过多来改变PCOS表型。
