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首页> 外文期刊>Archives of Neurology >Lack of an association of estrogen receptor alpha gene polymorphisms and transcriptional activity with Alzheimer disease.
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Lack of an association of estrogen receptor alpha gene polymorphisms and transcriptional activity with Alzheimer disease.

机译:缺乏雌激素受体α的协会基因多态性和转录活动阿尔茨海默病。

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BACKGROUND: Long-term cognitive decline in postmenopausal women is associated with aging and Alzheimer disease (AD). Estrogen replacement therapy has been reported to reduce the risk of developing AD. The distribution of estrogen receptors (ERs) in neurons overlaps that of the brain neurons known to develop AD. Estrogen increases the secretion and metabolism of amyloid precursor protein, may help synapse formation, and is reported to protect neurons from toxins. Restriction fragment length polymorphisms (RFLPs) of the ERalpha gene at intron 1 and exon 2 were associated with a low bone mineral density in postmenopausal women and also with AD in a Japanese population. OBJECTIVE: To determine whether ERalpha gene polymorphisms are associated with transcriptional activity and AD. METHODS: A luciferase reporter assay analyzed enhancer activity of the ERalpha gene at intron 1 and exon 2. This activity was evaluated according to the RFLPs. The RFLPs of the ERalpha gene were determined in Japanese patients clinically diagnosed as having AD, white patients diagnosed as having AD at autopsy, and corresponding healthy control subjects. The RFLPs were also evaluated for the contribution of the ERalpha gene RFLPs to AD. RESULTS: We found weak (about 2-fold) enhancer activity of the ERalpha gene, which differed among RFLPs. Although there were racial differences in these polymorphisms, we could not confirm the previously reported association between ERalpha gene polymorphisms and AD. CONCLUSION: Regulatory element of the ERalpha gene was found in intron 1, but we found no association between ERalpha gene polymorphisms and AD.
机译:背景:长期认知能力下降绝经后妇女与衰老和相关联阿尔茨海默病(AD)。治疗报道减少的风险开发广告。受体(人)在神经元的重叠大脑神经元发展广告。增加了淀粉样蛋白的分泌和代谢前体蛋白,有助于形成突触,据报道,和保护神经元免受毒素。限制片段长度多态性(rflp)ERalpha基因的内含子和外显子2 1低骨矿物质密度绝经后妇女,也与广告日本的人口。ERalpha基因多态性是否相关与转录活动和广告。荧光素酶报告实验分析增强剂活动ERalpha基因的内含子和外显子12. rflp。在日本病人临床决定诊断为广告,白色的病人诊断广告尸检,并对应健康对照组。评估ERalpha的贡献基因rflp广告。2倍)增强器ERalpha基因的活动,rflp之间的不同。种族差异在这些多态性,我们无法证实之前报道吗ERalpha基因多态性之间的联系和广告。ERalpha基因内含子1中被发现,但我们发现之间没有联系ERalpha基因多态性和广告。

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