Estrogen-metabolizing gene polymorphisms, but not estrogen receptor-α gene polymorphisms, are associated with the onset of menarche in healthy postmenopausal Japanese women
Estrogen-metabolizing gene polymorphisms, but not estrogen receptor-α gene polymorphisms, are associated with the onset of menarche in healthy postmenopausal Japanese women
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DOI：
10.1210/jc.2002-020353
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发表时间：
2003-02-01
影响因子：
5.8
通讯作者：
Hirahara, F
中科院分区：
文献类型：
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作者：
Gorai, I;Tanaka, K;Hirahara, F
月经开始和停止都有很强的遗传倾向。我们旨在通过研究雌激素受体-α和雌激素代谢酶基因的多态性来确定影响日本人群月经初潮和非自然绝经的遗传因素。317名年龄在46岁及以上的绝经后日本妇女在知情同意下参加了这项研究。提取外周血白细胞基因组DNA，采用限制性内切酶片段长度多态性分析方法检测雌激素受体α：PvuII、XbaI和雌激素代谢酶：细胞色素PYP17、雌激素生物合成(高活性A2/A2、细胞色素PYP1A1)、羟化(高诱导性，Vt/Vt和COMT)、失活(低活性，L/L)。各PvuII或XbaI基因及PvuII和XbaI基因的7种组合在月经初潮年龄、自然绝经年龄和月经年限方面均无显著差异。我们发现A1/A2基因携带者的月经初潮年龄明显早于A1/A1基因携带者(CyP17酶活性较高；13.6+/-1.2岁)；在自然绝经年龄和月经年限方面，不同的CYP17、CYP1A1或COMT基因型之间没有显著差异。由于每种雌激素代谢基因组合的样本量较小，因此不可能评估每种基因的相互依赖性，包括A2/A2L/LVt/Vt与A1/A1H/Hwt/wt等极端基因类型对月经初潮和/或自然绝经年龄的影响。结果表明，雌激素代谢的CYP17基因对健康绝经后日本妇女的初潮年龄有影响。
Both onset and cessation of menstruation have strong genetic inclination. We aimed to identify genetic factors influencing the onset of menarche and-natural menopause in a Japanese population by investigating the polymorphisms of estrogen receptor-alpha and estrogen-metabolizing enzyme genes. Three hundred seventeen postmenopausal Japanese women, aged 46 yr and over, were enrolled in this study under informed consent. Genomic DNA was extracted from peripheral leukocytes, and PCR-based restriction fragment length polymorphism assays were used to determine estrogen receptor-alpha: PvuII, XbaI, and estrogen-metabolizing enzymes; CYP17, estrogen biosynthesis (high activity, A2/A2, CYP1A1), hydroxylation (high inducibility, vt/vt, and COMT), inactivation (low activity, L/L) genotypes. There were no significant differences in ages at menarche and natural menopause or years of menstruation among each PvuII or XbaI genotype and seven combinations of PvuII and XbaI genotypes. We found that ages at menarche in women with A1/A2 (higher activity of CYP17; 13.6 +/- 1.2 yr) were significantly earlier than in those with A1/A1 (lower activity of CYP17; 14.1 +/- 1.3 yr). There were no significant differences in age at natural menopause and years of menstruation among each CYP17, CYP1A1, or COMT genotype. The small sample size of each combination of estrogen-metabolizing genotypes made it impractical to evaluate the effects of the interdependency of each genotype, including extreme genotype categories such as A2/A2L/Lvt/vt vs. A1/A1H/Hwt/wt genotypes, on ages at menarche and/or natural menopause. The results suggest that the estrogen-metabolizing CYP17 genotype influences age at menarche in healthy postmenopausal Japanese women.