Polymorphisms in the estrogen synthesis and metabolism pathways and symptoms during the menopausal transition: observations from the Seattle Midlife Women's Health Study
Polymorphisms in the estrogen synthesis and metabolism pathways and symptoms during the menopausal transition: observations from the Seattle Midlife Women's Health Study
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DOI：
10.1097/01.gme.0000227058.70903.9f
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发表时间：
2006-11-01
影响因子：
2.7
通讯作者：
Farin, Federico M.
中科院分区：
文献类型：
--
作者：
Woods, Nancy F.;Mitchell, Ellen Sullivan;Farin, Federico M.
目的：本研究的目的是确定雌激素合成和代谢途径的多态性是否与绝经过渡期妇女的血管痉挛症状有关。设计：2002年，一个自1990年以来参加西雅图中年妇女健康研究的妇女亚组（N = 174）提供了口腔涂片进行基因分型。1990年，通过对选定的多民族社区进行全面调查，招募了妇女。参与者是中年妇女，2005年平均年龄为53岁，受过良好教育，就业，已婚，代表多民族人口。对以下多态性进行基因分型：CYP 1Alm 2; CYP 1B 1 *2和CYP 1B 1 *3; CYP 17 5 'UTR; CYP 19 3' UTR; CYP 19（TTTA）n;包括CYP 19 7 r和CYP 19 7（r-3）; CYP 19 8 r和CYP 19 11 r;以及ESR 1 PvuII和ESR 1Xbal。女性在月经周期的第5、6和7天或每个月的固定日期对她们的血管紧张症状严重程度进行评估。根据每日月经日历确定月经过渡期。每年多次提供首次排尿尿液样本，测定雌酮葡萄糖醛酸苷。结果如下：CYP 19 11 r多态性的妇女在绝经中晚期过渡期和绝经后潮热更严重和频繁，在中晚期阶段E（1）G水平更高。研究的其他多态性均与潮热或雌酮葡萄糖醛酸苷水平无关。结论：这些研究结果表明，CYP 19多态性在绝经过渡期雌激素水平和血管痉挛症状中可能发挥作用，值得在更大和更多样化的女性人群中进一步研究。
Objective: The purpose of this study was to determine whether polymorphisms in the estrogen synthesis and metabolism pathways are associated with women's vasomotor symptom experiences during the menopausal transition. Design: In 2002, a subset of women enrolled in the Seattle Midlife Women's Health Study since 1990 (N = 174) provided a buccal smear for genotyping. Women were recruited by complete ascertainment of selected multiethnic neighborhoods in 1990. Participants were midlife women with a mean age of 53 years in 2005, well educated, employed, married, and represented a multiethnic population. Genotyping was done for the following polymorphisms: CYP1Alm2; CYP1B1*2 and CYP1B1*3; CYP17 5'UTR; CYP19 3'UTR; CYP19 (TTTA)n; including CYP19 7r and CYP19 7(r-3); CYP19 8r and CYP19 11r; and ESR1PvuII and ESR1Xbal. Women rated their vasomotor symptom severity in diaries on days 5, 6, and 7 of the menstrual cycle or on a constant date each month for women skipping periods. Menopausal transition stage was determined from daily menstrual calendars. First voided urine specimens provided several times each year were assayed for estrone glucuronide. Results: Women with the CYP19 11r polymorphism reported more severe and frequent hot flashes during the middle and late menopausal transition stages and postmenopause and higher E(1)G levels during middle and late stages. None of the other polymorphisms studied were related to hot flashes or to estrone glucuronide levels. Conclusions: These findings suggest a possible role for CYP19 polymorphisms in estrogen levels and in vasomotor symptoms during the menopausal transition that warrants further study in larger and more diverse populations of women.