title: Lack of an association of estrogen receptor alpha gene polymorphisms and transcriptional activity with Alzheimer disease.
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 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.
  
  
  CONCLUSIONS
  Regulatory element of the ERalpha gene was found in intron 1, but we found no association between ERalpha gene polymorphisms and AD.
authors.affiliation: Third Department of Internal Medicine, Hiroshima University School of Medicine, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Maruyama
authors.forename: H
authors.initials: H
authors.lastname: Toji
authors.forename: C R
authors.initials: CR
authors.lastname: Harrington
authors.forename: K
authors.initials: K
authors.lastname: Sasaki
authors.forename: Y
authors.initials: Y
authors.lastname: Izumi
authors.forename: T
authors.initials: T
authors.lastname: Ohnuma
authors.forename: H
authors.initials: H
authors.lastname: Arai
authors.forename: M
authors.initials: M
authors.lastname: Yasuda
authors.forename: C
authors.initials: C
authors.lastname: Tanaka
authors.forename: P C
authors.initials: PC
authors.lastname: Emson
authors.forename: S
authors.initials: S
authors.lastname: Nakamura
authors.forename: H
authors.initials: H
authors.lastname: Kawakami
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics*; D001057:Apolipoproteins E / Q000235:genetics; D044466:Asian People; D015519:Bone Density / Q000235:genetics; D017931:DNA Primers; D004742:Enhancer Elements, Genetic; D047628:Estrogen Receptor alpha; D005091:Exons / Q000235:genetics; D005260:Female; D017930:Genes, Reporter; D006801:Humans; D007438:Introns / Q000235:genetics; D008156:Luciferases / Q000235:genetics; D008297:Male; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics*; D012150:Polymorphism, Restriction Fragment Length; D011960:Receptors, Estrogen / Q000235:genetics*; D014158:Transcription, Genetic / Q000235:genetics*; D044465:White People
chemical_list: D001057:Apolipoproteins E; D017931:DNA Primers; D047628:Estrogen Receptor alpha; D011960:Receptors, Estrogen; D008156:Luciferases