The Journal of clinical endocrinology and metabolism · 2008
Association of CYP3A7*1C and serum dehydroepiandrosterone sulfate levels in women with polycystic ovary syndrome.
СтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Goodarzi Mark O, Xu Ning, Azziz Ricardo
Аннотация
CONTEXT: 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, CYP3A7*1C, which results in persistent expression in adults, was associated with reduced DHEAS levels in a previous study, which led us to consider CYP3A7*1C as a modulator of adrenal androgen excess in patients with PCOS.
OBJECTIVE: 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.
DESIGN: Women with and without PCOS were genotyped for CYP3A7*1C, and this variant was tested for association with DHEAS and total and free testosterone.
SETTING: 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).
PARTICIPANTS: A total of 287 white women with PCOS and 187 controls were studied.
MAIN MEASUREMENTS: CYP3A7*1C genotype, PCOS risk, and androgen levels were measured.
RESULTS: 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.
CONCLUSION: 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.
OBJECTIVE: 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.
DESIGN: Women with and without PCOS were genotyped for CYP3A7*1C, and this variant was tested for association with DHEAS and total and free testosterone.
SETTING: 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).
PARTICIPANTS: A total of 287 white women with PCOS and 187 controls were studied.
MAIN MEASUREMENTS: CYP3A7*1C genotype, PCOS risk, and androgen levels were measured.
RESULTS: 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.
CONCLUSION: 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.