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Aromatase Gene (CYP 19) Polymorphisms and Endogenous Androgen Concentrations in a Multiracial/Multiethnic, Multisite Study of Women at Midlife - 17/08/11

Doi : 10.1016/j.amjmed.2006.07.003 
MaryFran R. Sowers, PhD a, , Angela L. Wilson, MPH a, Sharon R. Kardia, PhD a, Jian Chu, MS a, Robert Ferrell, PhD b
a Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, Michigan, USA 
b Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, USA 

Requests 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.

Abstract

A limited number of studies have focused on androgens in women’s health, particularly at the genetic level. We evaluated testosterone and estradiol (E2) levels among women in relation to 5 single nucleotide polymorphisms (SNPs) of the aromatase (CYP 19) gene, the cytochrome P450 enzyme that converts androgens to estrogens. We related 5 aromatase SNPs (CYP 19 rs2414096, CYP 19 rs936306, CYP 19 rs2446405, CYP 19 rs1008805, and CYP 19 rs749292) to serum androgen and E2 markers in 1,538 participants of the Study of Women’s Health Across the Nation (SWAN), including 412 African American, 807 Caucasian, 151 Chinese, and 168 Japanese women. Aromatase allele and genotype frequencies differed significantly among racial/ethnic groups. Compared with other genotypes of the CYP 19 rs936306 polymorphism, the TT genotype was associated with a significant difference in the testosterone to E2 (T:E2) ratio—lower testosterone and higher E2 levels—especially in African American women. Japanese women with the AA genotype of the CYP 19 rs749292 polymorphism had lower testosterone and E2 levels but higher levels of sex hormone–binding globulin (SHBG) compared with Japanese women with the AG and GG genotypes. Among Caucasian women, there was markedly lower SHBG levels among those with the AA genotype of the CYP 19 rs2414096 polymorphism compared with other genotypes, after adjusting for age and body mass index. Three of 5 aromatase gene SNPs were associated with variation in serum androgen concentrations among women, both within and between racial/ethnic groups. Aromatase genetic markers may be important in understanding the emerging associations reported between endogenous androgens and women’s health status.

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Keywords : Androgens, Genetics, Sex hormones, Women


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 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.


© 2006  Elsevier Inc. Reservados todos los derechos.
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Vol 119 - N° 9S1

P. S23-S30 - septembre 2006 Regresar al número
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  • Endogenous Estradiol and Its Association with Estrogen Receptor Gene Polymorphisms
  • MaryFran R. Sowers, Mary L. Jannausch, Daniel S. McConnell, Sharon R. Kardia, John F. Randolph
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  • Menstrual Cycle Markers of Ovarian Aging and Sex Steroid Hormone Genotypes
  • MaryFran R. Sowers, Mary L. Jannausch, Daniel S. McConnell, Sharon R. Kardia, John F. Randolph

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