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Lack of an Association of Estrogen Receptor α Gene Polymorphisms and Transcriptional Activity With Alzheimer Disease

2000; American Medical Association; Volume: 57; Issue: 2 Linguagem: Inglês

10.1001/archneur.57.2.236

1538-3687

Hirofumi Maruyama, H Toji, Charles R. Harrington, Ken Sasaki, Yuishin Izumi, Tohru Ohnuma, Heii Arai, M. Yasuda, Chihiro Tanaka, P.C. Emson, Shigehisa Nakamura, Hideshi Kawakami,

Cancer-related cognitive impairment studies

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 ERα 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 ERα gene polymorphisms are associated with transcriptional activity and AD. Methods A luciferase reporter assay analyzed enhancer activity of the ERα gene at intron 1 and exon 2. This activity was evaluated according to the RFLPs. The RFLPs of the ERα 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 ERα gene RFLPs to AD. Results We found weak (about 2-fold) enhancer activity of the ERα gene, which differed among RFLPs. Although there were racial differences in these polymorphisms, we could not confirm the previously reported association between ERα gene polymorphisms and AD. Conclusion Regulatory element of the ERα gene was found in intron 1, but we found no association between ERα gene polymorphisms and AD.