Polymorphisms in CYP19A1, HSD17B1 and HSD17B2 genes and serum sex hormone level among postmenopausal Japanese women.
OBJECTIVE
Extraovarian sex hormone production plays an important role in estrogen biosynthesis in postmenopausal women. We examined possible associations between serum sex hormone level and polymorphisms in CYP19A1, HSD17B1, and HSD17B2. We also assessed possible interaction between these polymorphisms and current overweight.


METHODS
We conducted a cross-sectional study. 785 Japanese natural postmenopausal women were randomly selected from the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study database. Information on lifestyle factors was obtained from a self-administered questionnaire. Serum estrogens and androgens levels were measured by liquid chromatography-tandem mass spectrometry. Four tag SNPs (single nucleotide polymorphisms) of CYP19A1, one missense SNP of HSD17B1 and three tag SNPs of HSD17B2 were examined by Invader assay. A trend test was conducted using linear regression.


RESULTS
After adjustment for multiple comparisons, we found that rs4441215 and rs936306 in CYP19A1 and rs4888202 and rs2955160 in HSD17B2 were associated with differences in serum estrone level. Further, rs4441215 and rs936306 were associated with differences in serum estradiol level. None of these polymorphisms showed a significant interaction with current body mass index (BMI).


CONCLUSIONS
Our findings suggested that CYP19A1 and HSD17B2 polymorphisms might be associated with circulating sex hormone levels in Japanese postmenopausal women, independent of current BMI.
Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, 1-1 Kanokoden, Chikusa-ku, Nagoya 464-8681, Japan. Electronic address: shosono@aichi-cc.jp.
Satoyo
S
Hosono
Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, 1-1 Kanokoden, Chikusa-ku, Nagoya 464-8681, Japan.
Hidemi
H
Ito
Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, 1-1 Kanokoden, Chikusa-ku, Nagoya 464-8681, Japan.
Isao
I
Oze
Laboratory of Exercise Physiology, Faculty of Sports and Health Science, Fukuoka University, 8-19-1 Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan.
Yasuki
Y
Higaki
Department of Preventive Medicine, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan; Forestry and Forest Products Research Institute, 1 Matsunosato, Tsukuba, Ibaraki 305-8687, Japan.
Emi
E
Morita
Department of Health Science, Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu 520-2192, Japan.
Naoyuki
N
Takashima
Department of Public Health, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan.
Sadao
S
Suzuki
Department of International Islands and Community Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan.
Keiichi
K
Shimatani
Division of Cancer Registry, Prevention and Epidemiology, Chiba Cancer Center Research Institute, 666-2 Nitona-cho, Chuo-ku, Chiba 260-0801, Japan.
Haruo
H
Mikami
Department of Geriatric Medicine, Kyushu University Graduate School of Medical Sciences, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
Keizo
K
Ohnaka
Department of Epidemiology for Community Health and Medicine, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachihirokoji, Kamigyo-ku, Kyoto 602-8566, Japan.
Etsuko
E
Ozaki
Department of Preventive Medicine, Institute of Health Biosciences, The University of Tokushima Graduate School, 3-18-15, Kuramoto-cho, Tokushima 770-8503, Japan.
Sakurako
S
Katsuura-Kamano
Laboratory for Genotyping Development, Center for Genomic Medicine, RIKEN, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama 230-0045, Japan.
Michiaki
M
Kubo
Department of Epidemiology and Preventive Medicine, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu 501-1194, Japan.
Chisato
C
Nagata
Department of Preventive Medicine, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
Mariko
M
Naito
Department of Healthcare Administration, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
Nobuyuki
N
Hamajima
Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, 1-1 Kanokoden, Chikusa-ku, Nagoya 464-8681, Japan.
Hideo
H
Tanaka
D000368:Aged; D001141:Aromatase / Q000235:genetics*; D015992:Body Mass Index; D003430:Cross-Sectional Studies; D004958:Estradiol / Q000097:blood*; D004960:Estradiol Dehydrogenases / Q000235:genetics*; D004970:Estrone / Q000097:blood*; D005260:Female; D006801:Humans; D007564:Japan; D008875:Middle Aged; D050177:Overweight / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D017698:Postmenopause / Q000097:blood
D004970:Estrone; D004958:Estradiol; D004960:Estradiol Dehydrogenases; C513331:HSD17B1 protein, human; C523763:HSD17B2 protein, human; D001141:Aromatase; C561410:CYP19A1 protein, human
Cross-sectional study; Polymorphisms in CYP19A1, HSD17B1 and HSD17B2; Sex hormone concentration