Lack of an association of estrogen receptor alpha gene polymorphisms and transcriptional activity with Alzheimer disease

H Maruyama, H Toji, C R Harrington, K Sasaki, Y Izumi, T Ohnuma, H Arai, M Yasuda, C Tanaka, P C Emson, S Nakamura, H Kawakami

Research output: Contribution to journalArticle

Abstract

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 ER alpha 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 ER alpha gene polymorphisms are associated with transcriptional activity and AD.

Methods: A luciferase reporter assay analyzed enhancer activity of the ER alpha gene at intron 1 and exon 2. This activity was evaluated according to the RFLPs. The RFLPs of the ER alpha 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 ER alpha gene RFLPs to AD.

Results: We found weak (about 2-fold) enhancer activity of the ER alpha gene, which differed among RFLPs. Although there were racial differences in these polymorphisms, we could not confirm the previously reported association between ER alpha, gene polymorphisms and AD.

Conclusion: Regulatory element of the ER alpha gene was found in intron 1, but we found no association between ER alpha gene polymorphisms and AD.

Original languageEnglish
Pages (from-to)236-240
Number of pages5
JournalArchives of Neurology
Volume57
Publication statusPublished - 2000

Keywords

  • APOLIPOPROTEIN-E GENOTYPE
  • REPLACEMENT THERAPY
  • CHOLINERGIC NEURONS
  • BASAL FOREBRAIN
  • SELECTIVE LOSS
  • BREAST-CANCER
  • OLDER WOMEN
  • EXPRESSION
  • LUCIFERASE
  • MENOPAUSE

Cite this

Lack of an association of estrogen receptor alpha gene polymorphisms and transcriptional activity with Alzheimer disease. / Maruyama, H ; Toji, H ; Harrington, C R ; Sasaki, K ; Izumi, Y ; Ohnuma, T ; Arai, H ; Yasuda, M ; Tanaka, C ; Emson, P C ; Nakamura, S ; Kawakami, H .

In: Archives of Neurology, Vol. 57, 2000, p. 236-240.

Research output: Contribution to journalArticle

Maruyama, H, Toji, H, Harrington, CR, Sasaki, K, Izumi, Y, Ohnuma, T, Arai, H, Yasuda, M, Tanaka, C, Emson, PC, Nakamura, S & Kawakami, H 2000, 'Lack of an association of estrogen receptor alpha gene polymorphisms and transcriptional activity with Alzheimer disease', Archives of Neurology, vol. 57, pp. 236-240.
Maruyama, H ; Toji, H ; Harrington, C R ; Sasaki, K ; Izumi, Y ; Ohnuma, T ; Arai, H ; Yasuda, M ; Tanaka, C ; Emson, P C ; Nakamura, S ; Kawakami, H . / Lack of an association of estrogen receptor alpha gene polymorphisms and transcriptional activity with Alzheimer disease. In: Archives of Neurology. 2000 ; Vol. 57. pp. 236-240.
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abstract = "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 ER alpha 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 ER alpha gene polymorphisms are associated with transcriptional activity and AD.Methods: A luciferase reporter assay analyzed enhancer activity of the ER alpha gene at intron 1 and exon 2. This activity was evaluated according to the RFLPs. The RFLPs of the ER alpha 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 ER alpha gene RFLPs to AD.Results: We found weak (about 2-fold) enhancer activity of the ER alpha gene, which differed among RFLPs. Although there were racial differences in these polymorphisms, we could not confirm the previously reported association between ER alpha, gene polymorphisms and AD.Conclusion: Regulatory element of the ER alpha gene was found in intron 1, but we found no association between ER alpha gene polymorphisms and AD.",
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T1 - Lack of an association of estrogen receptor alpha gene polymorphisms and transcriptional activity with Alzheimer disease

AU - Maruyama, H

AU - Toji, H

AU - Harrington, C R

AU - Sasaki, K

AU - Izumi, Y

AU - Ohnuma, T

AU - Arai, H

AU - Yasuda, M

AU - Tanaka, C

AU - Emson, P C

AU - Nakamura, S

AU - Kawakami, H

PY - 2000

Y1 - 2000

N2 - 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 ER alpha 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 ER alpha gene polymorphisms are associated with transcriptional activity and AD.Methods: A luciferase reporter assay analyzed enhancer activity of the ER alpha gene at intron 1 and exon 2. This activity was evaluated according to the RFLPs. The RFLPs of the ER alpha 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 ER alpha gene RFLPs to AD.Results: We found weak (about 2-fold) enhancer activity of the ER alpha gene, which differed among RFLPs. Although there were racial differences in these polymorphisms, we could not confirm the previously reported association between ER alpha, gene polymorphisms and AD.Conclusion: Regulatory element of the ER alpha gene was found in intron 1, but we found no association between ER alpha gene polymorphisms and AD.

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

KW - APOLIPOPROTEIN-E GENOTYPE

KW - REPLACEMENT THERAPY

KW - CHOLINERGIC NEURONS

KW - BASAL FOREBRAIN

KW - SELECTIVE LOSS

KW - BREAST-CANCER

KW - OLDER WOMEN

KW - EXPRESSION

KW - LUCIFERASE

KW - MENOPAUSE

M3 - Article

VL - 57

SP - 236

EP - 240

JO - Archives of Neurology

JF - Archives of Neurology

SN - 0003-9942

ER -