title: Association of estrogen receptor alpha gene polymorphisms with neurofibrillary tangles.
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.affiliation: Department of Endocrinology, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan. hakazama@h4.dion.ne.jp
authors.forename: Hirohito
authors.initials: H
authors.lastname: Kazama
authors.forename: Nyoka N
authors.initials: NN
authors.lastname: Ruberu
authors.forename: Shigeo
authors.initials: S
authors.lastname: Murayama
authors.forename: Yuko
authors.initials: Y
authors.lastname: Saito
authors.forename: Ken-Ichi
authors.initials: K
authors.lastname: Nakahara
authors.forename: Kazutomi
authors.initials: K
authors.lastname: Kanemaru
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nagura
authors.forename: Tomio
authors.initials: T
authors.lastname: Arai
authors.forename: Motoji
authors.initials: M
authors.lastname: Sawabe
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yamanouchi
authors.forename: Hajime
authors.initials: H
authors.lastname: Orimo
authors.forename: Takayuki
authors.initials: T
authors.lastname: Hosoi
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000544:Alzheimer Disease / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000235:genetics; D001921:Brain / Q000473:pathology; D018450:Disease Progression; D047628:Estrogen Receptor alpha / Q000235:genetics*; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D006580:Genetic Carrier Screening; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D016874:Neurofibrillary Tangles / Q000235:genetics* / Q000473:pathology; D058225:Plaque, Amyloid / Q000235:genetics / Q000473:pathology; D011110:Polymorphism, Genetic / Q000235:genetics*; D014041:Tokyo
chemical_list: D053327:Apolipoprotein E4; D001057:Apolipoproteins E; D047628:Estrogen Receptor alpha