Association of CYP3A7*1C and serum dehydroepiandrosterone sulfate levels in women with polycystic ovary syndrome.
BACKGROUND
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.


METHODS
Women with and without PCOS were genotyped for CYP3A7*1C, and this variant was tested for association with DHEAS and total and free testosterone.


METHODS
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).


METHODS
A total of 287 white women with PCOS and 187 controls were studied.


METHODS
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.


CONCLUSIONS
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.
Goodarzi
Mark O
MO
Department of Obstetrics/Gynecology and Center for Androgen Related Disorders, Cedars-Sinai Medical Center, 8635 West Third Street, Los Angeles, CA 90048, USA.
Xu
Ning
N
Azziz
Ricardo
R
D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics* / Q000378:metabolism; D051544:Cytochrome P-450 CYP3A; D019314:Dehydroepiandrosterone Sulfate / Q000097:blood*; D005260:Female; D005838:Genotype; D006801:Humans; D011085:Polycystic Ovary Syndrome / Q000097:blood* / Q000235:genetics*; D013739:Testosterone / Q000097:blood
D013739:Testosterone; D019314:Dehydroepiandrosterone Sulfate; D001189:Aryl Hydrocarbon Hydroxylases; C103123:CYP3A7 protein, human; D051544:Cytochrome P-450 CYP3A