Association between CYP19A1 polymorphisms and sex hormones in postmenopausal Japanese women
Association between CYP19A1 polymorphisms and sex hormones in postmenopausal Japanese women
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DOI：
10.1038/jhg.2008.11
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发表时间：
2009-02-01
影响因子：
3.5
通讯作者：
Matsuo, Keitaro
中科院分区：
文献类型：
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作者：
Kidokoro, Kumiko;Ino, Kazuhiko;Matsuo, Keitaro
在绝经后妇女中，卵巢外性激素的产生在荷尔蒙相关疾病中发挥着重要作用，如乳腺癌和子宫内膜癌。芳香酶是由CYP19A1编码的一种酶，是参与雌激素生物合成的关键酶。在日本人群中，CYP19A1基因多态性对血清性激素水平的影响从未被调查过。这项研究招募了100名绝经后未患癌症的日本女性。确定了25个CYP19A1基因座，测量了血清性激素水平；收集了生活方式数据，即雌酮(E1)、雌二醇(E2)、睾酮和性激素结合球蛋白(SHBG)。我们进行了一项横断面分析，以评估CYP19A1单倍型对血清性激素水平的影响。研究发现，体重指数为25 kg/m(2)的受试者在循环睾酮水平上有显著差异(0.29+/-0.19，P=0.050)。年龄、体育运动量或饮酒习惯都没有对激素水平产生任何影响。通过LD分析，我们确定了CYP19A1的7个单倍型区块。雌酮水平在rs12148604(SNP 1)和rs11632903(SNP14)中不同。未观察到雌二醇的显著基因座。SHBG水平与rs4441215(SNP11)相关。睾酮水平与rs752760(SNP24)和rs2445768(SNP25)密切相关，与SNP1、SNP11和SNP14弱相关。我们发现，CYP19A1基因的多态影响日本绝经后妇女的性激素水平。
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 >= 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.