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Association of estrogen receptor alpha gene polymorphisms with neurofibrillary tangles.
Dement Geriatr Cogn Disord. 2004; 18(2):145-50.DG

Abstract

Estrogen receptor alpha (ERalpha) may be implicated in the pathogenesis of Alzheimer's disease (AD). The aim of this study was to clarify the association between ERalpha gene polymorphisms and AD-related pathologic changes. The staging of neurofibrillary tangles (NFT) and senile plaques (SP) was performed according to the method by Braak and Braak and two polymorphisms, PvuII (P or p) and XbaI (X or x), of the ERalpha gene were typed in 551 Japanese cadavers (294 men and 257 women; mean age, 80.8 years). Distributions of the NFT and SP stages significantly correlated with age (NFT: r = 0.306, p < 0.0001; SP: r = 0.237, p < 0.0001) and were significantly higher in patients with the apolipoprotein E epsilon4 allele (p < 0.0001). Possession of the P allele showed a trend to be associated with a more serious NFT stage, but had no relationship with the SP stage. In men, a significant association between PvuII polymorphism and the NFT stage (p = 0.002) was found, revealing a gene- dose effect of the P allele. Similar results were obtained in the men without the epsilon4 allele (p = 0.011). Multiple regression analyses demonstrated that age was the strongest determinant of the NFT stage, possession of the epsilon4 allele was the next strongest, and PvuII polymorphism was the third strongest (p < 0.0001, R(2) = 0.144). The XbaI polymorphism did affect neither the NFT stage nor the SP stage. In conclusion, the PvuII polymorphism of the ERalpha gene is associated with Braak NFT stages and possession of the P allele may act as a risk factor for AD in Japanese men, especially in those without the epsilon4 allele.

Authors+Show Affiliations

Department of Endocrinology, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan. hakazama@h4.dion.ne.jpNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article

Language

eng

PubMed ID

15211069

Citation

Kazama, Hirohito, et al. "Association of Estrogen Receptor Alpha Gene Polymorphisms With Neurofibrillary Tangles." Dementia and Geriatric Cognitive Disorders, vol. 18, no. 2, 2004, pp. 145-50.
Kazama H, Ruberu NN, Murayama S, et al. Association of estrogen receptor alpha gene polymorphisms with neurofibrillary tangles. Dement Geriatr Cogn Disord. 2004;18(2):145-50.
Kazama, H., Ruberu, N. N., Murayama, S., Saito, Y., Nakahara, K., Kanemaru, K., Nagura, H., Arai, T., Sawabe, M., Yamanouchi, H., Orimo, H., & Hosoi, T. (2004). Association of estrogen receptor alpha gene polymorphisms with neurofibrillary tangles. Dementia and Geriatric Cognitive Disorders, 18(2), 145-50.
Kazama H, et al. Association of Estrogen Receptor Alpha Gene Polymorphisms With Neurofibrillary Tangles. Dement Geriatr Cogn Disord. 2004;18(2):145-50. PubMed PMID: 15211069.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Association of estrogen receptor alpha gene polymorphisms with neurofibrillary tangles. AU - Kazama,Hirohito, AU - Ruberu,Nyoka N, AU - Murayama,Shigeo, AU - Saito,Yuko, AU - Nakahara,Ken-Ichi, AU - Kanemaru,Kazutomi, AU - Nagura,Hiroshi, AU - Arai,Tomio, AU - Sawabe,Motoji, AU - Yamanouchi,Hiroshi, AU - Orimo,Hajime, AU - Hosoi,Takayuki, Y1 - 2004/06/18/ PY - 2003/12/19/accepted PY - 2004/6/24/pubmed PY - 2005/2/3/medline PY - 2004/6/24/entrez SP - 145 EP - 50 JF - Dementia and geriatric cognitive disorders JO - Dement Geriatr Cogn Disord VL - 18 IS - 2 N2 - Estrogen receptor alpha (ERalpha) may be implicated in the pathogenesis of Alzheimer's disease (AD). The aim of this study was to clarify the association between ERalpha gene polymorphisms and AD-related pathologic changes. The staging of neurofibrillary tangles (NFT) and senile plaques (SP) was performed according to the method by Braak and Braak and two polymorphisms, PvuII (P or p) and XbaI (X or x), of the ERalpha gene were typed in 551 Japanese cadavers (294 men and 257 women; mean age, 80.8 years). Distributions of the NFT and SP stages significantly correlated with age (NFT: r = 0.306, p < 0.0001; SP: r = 0.237, p < 0.0001) and were significantly higher in patients with the apolipoprotein E epsilon4 allele (p < 0.0001). Possession of the P allele showed a trend to be associated with a more serious NFT stage, but had no relationship with the SP stage. In men, a significant association between PvuII polymorphism and the NFT stage (p = 0.002) was found, revealing a gene- dose effect of the P allele. Similar results were obtained in the men without the epsilon4 allele (p = 0.011). Multiple regression analyses demonstrated that age was the strongest determinant of the NFT stage, possession of the epsilon4 allele was the next strongest, and PvuII polymorphism was the third strongest (p < 0.0001, R(2) = 0.144). The XbaI polymorphism did affect neither the NFT stage nor the SP stage. In conclusion, the PvuII polymorphism of the ERalpha gene is associated with Braak NFT stages and possession of the P allele may act as a risk factor for AD in Japanese men, especially in those without the epsilon4 allele. SN - 1420-8008 UR - https://www.unboundmedicine.com/medline/citation/15211069/Association_of_estrogen_receptor_alpha_gene_polymorphisms_with_neurofibrillary_tangles_ L2 - https://www.karger.com?DOI=10.1159/000079194 DB - PRIME DP - Unbound Medicine ER -