The American Journal of Medicine
Volume 119, Issue 9, Supplement 1 , Pages S23-S30 , September 2006

Aromatase Gene (CYP 19) Polymorphisms and Endogenous Androgen Concentrations in a Multiracial/Multiethnic, Multisite Study of Women at Midlife

  • MaryFran R. Sowers, PhD

      Affiliations

    • Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, Michigan, USA
    • Corresponding Author InformationRequests for reprints should be addressed to MaryFran R. Sowers, PhD, 339 East Liberty, Suite 310, School of Public Health, University of Michigan, Ann Arbor, Michigan 48104.
  • ,
  • Angela L. Wilson, MPH

      Affiliations

    • Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, Michigan, USA
  • ,
  • Sharon R. Kardia, PhD

      Affiliations

    • Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, Michigan, USA
  • ,
  • Jian Chu, MS

      Affiliations

    • Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, Michigan, USA
  • ,
  • Robert Ferrell, PhD

      Affiliations

    • Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, USA

References 

  1. Griffin JE , Wilson JD . Disorders of the testes and the male reproductive tract . In:  Williams RH ,  Larsen PR ,  Kronenberg HM ,  Melmed S ,  Polonsky KS editor. Williams Textbook of Endocrinology . 10th ed.. Philadelphia: WB Saunders; 2003;p. 715
  2. Dhatariya KK , Nair K . Dehydroepiandrosterone: is there a role for replacement? . Mayo Clin Proc . 2003;78:1257–1273
  3. Bulun SE , Sebastian S , Takayama K , Suzuki T , Sasano H , Shozu M . The human CYP 19 (aromatase P450) gene: update on physiologic roles and genomic organization of promoters . J Steroid Biochem Mol Biol . 2003;86:219–224
  4. Meinhardt U , Mullis PE . The essential role of the aromatase/p450arom . Semin Reprod Med . 2002;20:277–283
  5. Bulun SE , Takayama K , Suzuki T , Sasano H , Yilmaz B , Sebastian S . Organization of the human aromatase P450 (CYP19) gene . Semin Reprod Med . 2004;22:5–9
  6. Fisher CR , Graves KH , Parlow AF , Simpson ER . Characterization of mice deficient in aromatase (ArKO) because of targeted disruption of the CYP19 gene . Proc Natl Acad Sci U S A . 1998;95:6965–6970
  7. Britt KL , Drummond AE , Dyson M , et al.   The ovarian phenotype of the aromatase knockout (ArKO) mouse . J Steroid Biochem Mol Biol . 2001;79:181–185
  8. Ito Y , Fisher CR , Conte FA , Grumbach MM , Simpson ER . Molecular basis of aromatase deficiency in an adult female with sexual infantilism and polycystic ovaries . Proc Natl Acad Sci U S A . 1993;90:11673–11677
  9. Morishima A , Grumbach MM , Simpson ER , Fisher C , Qin K . Aromatase deficiency in male and female siblings caused by a novel mutation and the physiological role of estrogens . J Clin Endocrinol Metab . 1995;80:3689–3698
  10. Mullis PE , Yoshimura N , Kuhlmann B , Lippunder K , Jaeger P , Harada H . Aromatase deficiency in a female who is compound heterozygote for two new point mutations in the P450arom gene: impact of estrogens on hypergonadotropic hypogonadism, multicystic ovaries and bone densitometry in childhood . J Clin Endocrinol Metab . 1997;82:1739–1745
  11. Belgorosky A , Pepe C , Marino R , et al.   Hypothalamic-pituitary-ovarian axis during infancy, early and late prepuberty in an aromatase-deficient girl who is a compound heterozygote for two new point mutations of the CYP19 gene . J Clin Endocrinol Metab . 2003;88:5127–5131
  12. Berstein LM , Imyanitov EN , Suspitsin EN , et al.   CYP19 gene polymorphism in endometrial cancer patients . J Cancer Res Clin Oncol . 2001;127:135–138
  13. Dunning AM , Dowsett M , Healey CS , et al.   Polymorphisms associated with circulating sex hormone in postmenopausal women . J Natl Cancer Inst . 2004;96:936–945
  14. Tworoger SS , Chubak J , Aiello EJ , et al.   Association of CYP17, CYP19, CYP1B1, and COMT polymorphisms with serum and urinary sex hormone concentrations in postmenopausal women . Cancer Epidemiol Biomarkers Prev . 2004;13:94–101
  15. Single Nucleotide Polymorphism database: dbSNP search page. National Center for Biotechnology Information Web site. Available at: http://www.ncbi.nlm.nih.gov/SNP/. Accessed September 23, 2005.
  16. Sowers MF , Crawford S , Sternfeld B , et al.   Design, survey sampling and recruitment methods of SWAN: a multicenter, multiethnic, community-based cohort study of women and the menopausal transition . In:  Lobo RA ,  Kelsey J ,  Marcus R editor. Menopause: Biology and Pathobiology . San Diego, CA: Academic Press; 2000;p. 175–188
  17. Kardia SR , Chu J , Sowers MF , et al.   Characterizing variation in sex steroid hormone pathway genes in women of 4 races/ethnicities: the Study of Women’s Health Across the Nation (SWAN) . Am J Med . 2006;119(suppl 9A):S3–S15
  18. Haiman CA , Stram DO , Pike MC , et al.   A comprehensive haplotype analysis of CYP19 and breast cancer risk: the Multiethnic Cohort . Hum Mol Genet . 2003;12:2679–2692
  19. Ferris BG . Epidemiology Standardization Project (American Thoracic Society) . Am Rev Respir Dis . 1978;188:1–120
  20. Beer DG , Kardia SLR , Huang C-C , et al.   Gene-expression profiles predict survival of patients with lung adenocarcinoma . Nat Med . 2002;8:816–824
  21. Buster JE , Casson PR . DHEA: biology and use in therapeutic intervention . In:  Lobo RA ,  Kelsey J ,  Marcus R editor. Menopause: Biology and Pathobiology . San Diego, CA: Academic Press; 2000;p. 625–638
  22. Simpson E , Rubin G , Clyne C , et al.   The role of local estrogen biosynthesis in males and females . Trends Endocrinol Metab . 2000;11:184–188
  23. Labrie F , Bélanger A , Cusan L , Gomez JL , Candas B . Marked decline in serum concentrations of adrenal C19 sex steroid precursors and conjugated androgen metabolites during aging . J Clin Endocrinol Metab . 1997;82:2396–2402
  24. Haiman CA , Hankinson SE , Spiegelman D , et al.   A tetranucleotide repeat polymorphism in CYP19 and breast cancer risk . Int J Cancer . 2000;87:204–210
  25. Davison SL , Davis SR . Androgens in women . J Steroid Biochem Mol Biol . 2003;85:363–366
  26. Key T , Appleby P , Barnes I , Reeves G  Endogenous Hormones and Breast Cancer Collaborative Group . Endogenous sex hormones and breast cancer in postmenopausal women: reanalysis of nine prospective studies . J Natl Cancer Inst . 2002;94:606–616

 The Study of Women’s Health Across the Nation (SWAN) and the SWAN Repository were supported by grants from the National Institutes of Health (NIH), Department of Health and Human Services, through the National Institute on Aging, the National Institute of Nursing Research, and the NIH Office of Research on Women’s Health (Grant Nos. AG017719, NR004061, AG012505, AG012535, AG012531, AG012539, AG012546, AG012553, AG012554, and AG012495). The Sex Steroid Hormone Genetics Protocol was supported by the SWAN Repository.This report is based on samples from the SWAN DNA Repository. Scientists interested in developing studies based on this resource can find a description of the SWAN Core Repository and DNA Repository and information on obtaining access to the resources at www.swanrepository.org.

PII: S0002-9343(06)00825-4

doi: 10.1016/j.amjmed.2006.07.003

The American Journal of Medicine
Volume 119, Issue 9, Supplement 1 , Pages S23-S30 , September 2006