title: Association of estrogen receptor alpha (ESR1) PvuII and XbaI polymorphisms with sporadic Alzheimer's disease and their effect on apolipoprotein E concentrations.
abstract: BACKGROUND
  Many studies have shown that estrogen replacement therapy may improve cognitive function in women and reduce the risk of Alzheimer's disease (AD). Because most of the estrogen neuroprotective effect is mediated by receptors, we studied the associations between estrogen receptor alpha (ESR1) polymorphisms (PvuII and XbaI) and AD, and their interactions with apolipoprotein E (APOE) polymorphism and plasma levels.
  
  
  METHODS
  ESR1 genotypes and APOE plasma concentrations were determined in a sample of AD patients and controls.
  
  
  RESULTS
  ESR1 PP and XX genotypes were associated with an increased risk for AD only in males (OR = 3.6, 95% CI = 1.2-10.9) and conferred a relevant additional risk of AD to subjects also carrying APOE e*4 allele (OR = 13.3, 95% CI = 1.7-103.6). Mean APOE concentrations were lower in AD patients; the lowest levels were observed in male patients carrying PP and/or XX genotypes (p = 0.006) and in patients carrying PP and/or XX genotypes together with the e*4 allele (p = 0.003). In AD women, ESR1 PP and XX genotypes were also associated with lower MMSE values (p = 0.0007).
  
  
  CONCLUSIONS
  The present data suggest that the involvement of ESR1 polymorphisms in AD onset is mediated by the regulation of apoE expression. ESR1 polymorphisms are also associated with a faster cognitive decline in the women AD patients.
authors.affiliation: Department of Genetics and Molecular Biology, University 'La Sapienza', Rome, Italy. Rosamaria.corbo@uniroma1.it
authors.forename: Rosa Maria
authors.initials: RM
authors.lastname: Corbo
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Gambina
authors.forename: Maria
authors.initials: M
authors.lastname: Ruggeri
authors.forename: Renato
authors.initials: R
authors.lastname: Scacchi
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000235:genetics* / Q000523:psychology; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000097:blood / Q000378:metabolism*; D004247:DNA / Q000235:genetics; D047628:Estrogen Receptor alpha / Q000235:genetics*; D005260:Female; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008297:Male; D009483:Neuropsychological Tests; D011110:Polymorphism, Genetic / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012307:Risk Factors
chemical_list: D053327:Apolipoprotein E4; D001057:Apolipoproteins E; D047628:Estrogen Receptor alpha; D004247:DNA