Aromatase gene (CYP 19) polymorphisms and endogenous androgen concentrations in a multiracial/multiethnic, multisite study of women at midlife.
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.
Sowers
MaryFran R
MR
Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, Michigan 48104, USA. mfsowers@umich.edu
Wilson
Angela L
AL
Kardia
Sharon R
SR
Chu
Jian
J
Ferrell
Robert
R
D000328:Adult; D000728:Androgens / Q000097:blood* / Q000378:metabolism; D001141:Aromatase / Q000235:genetics* / Q000378:metabolism; D004958:Estradiol / Q000378:metabolism; D005260:Female; D006801:Humans; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D044469:Racial Groups / Q000235:genetics*; D012738:Sex Hormone-Binding Globulin / Q000378:metabolism; D013739:Testosterone / Q000097:blood
D000728:Androgens; D012738:Sex Hormone-Binding Globulin; D013739:Testosterone; D004958:Estradiol; D001141:Aromatase