title: Association of CYP3A7*1C and serum dehydroepiandrosterone sulfate levels in women with polycystic ovary syndrome.
abstract: 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.
authors.affiliation: Department of Obstetrics/Gynecology and Center for Androgen Related Disorders, Cedars-Sinai Medical Center, 8635 West Third Street, Los Angeles, CA 90048, USA.
authors.forename: Mark O
authors.initials: MO
authors.lastname: Goodarzi
authors.forename: Ning
authors.initials: N
authors.lastname: Xu
authors.forename: Ricardo
authors.initials: R
authors.lastname: Azziz
mesh_terms: 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
chemical_list: D013739:Testosterone; D019314:Dehydroepiandrosterone Sulfate; D001189:Aryl Hydrocarbon Hydroxylases; C103123:CYP3A7 protein, human; D051544:Cytochrome P-450 CYP3A