Association between CYP19A1 polymorphisms and sex hormones in postmenopausal Japanese women.
In postmenopausal women, extraovarian sex hormone production plays an important role in hormone-related diseases, such as breast and endometrial cancers. Aromatase, an enzyme encoded by CYP19A1, is a key enzyme involved in estrogen biosynthesis. The impact of CYP19A1 polymorphisms on serum sex hormone levels in the Japanese population has never been investigated. This study enrolled 100 postmenopausal Japanese women found to be without cancer. Twenty-five CYP19A1 loci were identified, and measurements were conducted on serum levels of sex hormones; lifestyle data were collected, namely estrone (E1), estradiol (E2), testosterone and sex hormone-binding globulin (SHBG). We conducted a cross-sectional analysis to evaluate the impact of CYP19A1 haplotype on serum sex hormone levels. We found that subjects with BMI>or=25 kg/m(2) showed a significant difference in circulating testosterone levels (0.29+/-0.19, P=0.050). Neither age nor the amount of physical exercise or drinking habits showed any effect on hormone levels. We identified seven haplotype blocks in CYP19A1 by LD analysis. Estrone levels differed in rs12148604 (SNP 1) and rs11632903 (SNP14). No significant locus for estradiol was observed. SHBG levels were associated with rs4441215 (SNP11). Testosterone levels were strongly associated with rs752760 (SNP24) and rs2445768 (SNP25) and weakly associated with SNP 1, SNP11 and SNP14 as well. We found that polymorphisms in CYP19A1 influence sex hormone levels in Japanese postmenopausal women.
Kidokoro
Kumiko
K
Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya, Japan.
Ino
Kazuhiko
K
Hirose
Kaoru
K
Kajiyama
Hiroaki
H
Hosono
Satoyo
S
Suzuki
Takeshi
T
Kawase
Takakazu
T
Hiraki
Akio
A
Hamajima
Nobuyuki
N
Tanaka
Hideo
H
Tajima
Kazuo
K
Kikkawa
Fumitaka
F
Matsuo
Keitaro
K
D000368:Aged; D000369:Aged, 80 and over; D001141:Aromatase / Q000235:genetics*; D044466:Asian People / Q000235:genetics*; D004970:Estrone / Q000097:blood; D005260:Female; D056426:Genetic Loci / Q000235:genetics; D012739:Gonadal Steroid Hormones / Q000097:blood* / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D007564:Japan; D015810:Linkage Disequilibrium / Q000235:genetics; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D017698:Postmenopause / Q000097:blood* / Q000235:genetics*; D012738:Sex Hormone-Binding Globulin / Q000032:analysis; D013739:Testosterone / Q000097:blood
D012739:Gonadal Steroid Hormones; D012738:Sex Hormone-Binding Globulin; D004970:Estrone; D013739:Testosterone; D001141:Aromatase