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绝经后日本女性中CYP19A1、HSD17B1和HSD17B2基因多态性与血清性激素水平

Polymorphisms in CYP19A1, HSD17B1 and HSD17B2 genes and serum sex hormone level among postmenopausal Japanese women.

作者信息

Hosono Satoyo, Ito Hidemi, Oze Isao, Higaki Yasuki, Morita Emi, Takashima Naoyuki, Suzuki Sadao, Shimatani Keiichi, Mikami Haruo, Ohnaka Keizo, Ozaki Etsuko, Katsuura-Kamano Sakurako, Kubo Michiaki, Nagata Chisato, Naito Mariko, Hamajima Nobuyuki, Tanaka Hideo

机构信息

Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, 1-1 Kanokoden, Chikusa-ku, Nagoya 464-8681, Japan.

Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, 1-1 Kanokoden, Chikusa-ku, Nagoya 464-8681, Japan.

出版信息

Maturitas. 2015 Dec;82(4):394-401. doi: 10.1016/j.maturitas.2015.08.003. Epub 2015 Aug 13.

DOI:10.1016/j.maturitas.2015.08.003
PMID:26323233
Abstract

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.

摘要

目的

卵巢外性激素生成在绝经后女性雌激素生物合成中起重要作用。我们研究了血清性激素水平与CYP19A1、HSD17B1和HSD17B2基因多态性之间的可能关联。我们还评估了这些多态性与当前超重之间的可能相互作用。

方法

我们进行了一项横断面研究。从日本多机构合作队列(J-MICC)研究数据库中随机选取785名日本自然绝经后女性。生活方式因素信息通过自填问卷获得。采用液相色谱-串联质谱法测定血清雌激素和雄激素水平。通过Invader分析检测CYP19A1的4个标签单核苷酸多态性(SNP)、HSD17B1的1个错义SNP和HSD17B2的3个标签SNP。使用线性回归进行趋势检验。

结果

在进行多重比较校正后,我们发现CYP19A1中的rs4441215和rs936306以及HSD17B2中的rs4888202和rs2955160与血清雌酮水平差异相关。此外,rs4441215和rs936306与血清雌二醇水平差异相关。这些多态性均未显示与当前体重指数(BMI)有显著相互作用。

结论

我们的研究结果表明,CYP19A1和HSD17B2基因多态性可能与日本绝经后女性的循环性激素水平相关,且独立于当前BMI。

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