title: Estrogen receptor-Beta variants are associated with increased risk of Alzheimer's disease in women with down syndrome.
abstract: OBJECTIVE
  Genetic variants that affect estrogen activity may influence the risk of Alzheimer's disease (AD). We examined the relation of polymorphisms in the gene for the estrogen receptor-beta (ESR2) to the risk of AD in women with Down syndrome.
  
  
  METHODS
  Two hundred and forty-nine women with Down syndrome, 31-70 years of age and nondemented at baseline, were followed at 14- to 18-month intervals for 4 years. Women were genotyped for 13 single-nucleotide polymorphisms (SNPs) in the ESR2 gene, and their association with AD incidence was examined.
  
  
  RESULTS
  Among postmenopausal women, we found a 2-fold increase in the risk of AD for women carrying 1 or 2 copies of the minor allele at 3 SNPs in introns seven (rs17766755) and six (rs4365213 and rs12435857) and 1 SNP in intron eight (rs4986938) of ESR2.
  
  
  CONCLUSIONS
  These findings support a role for estrogen and its major brain receptors in modulating susceptibility to AD in women.
authors.affiliation: Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Medical Center, G.H. Sergievsky Center, New York, N.Y., USA.
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhao
authors.forename: Joseph H
authors.initials: JH
authors.lastname: Lee
authors.forename: Deborah
authors.initials: D
authors.lastname: Pang
authors.forename: Alexis
authors.initials: A
authors.lastname: Temkin
authors.forename: Naeun
authors.initials: N
authors.lastname: Park
authors.forename: Sarah C
authors.initials: SC
authors.lastname: Janicki
authors.forename: Warren B
authors.initials: WB
authors.lastname: Zigman
authors.forename: Wayne
authors.initials: W
authors.lastname: Silverman
authors.forename: Benjamin
authors.initials: B
authors.lastname: Tycko
authors.forename: Nicole
authors.initials: N
authors.lastname: Schupf
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D000544:Alzheimer Disease / Q000150:complications* / Q000235:genetics*; D001057:Apolipoproteins E / Q000235:genetics; D015992:Body Mass Index; D015331:Cohort Studies; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D003704:Dementia / Q000145:classification / Q000523:psychology; D004314:Down Syndrome / Q000150:complications* / Q000453:epidemiology / Q000235:genetics*; D047629:Estrogen Receptor beta / Q000235:genetics*; D005006:Ethnicity; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008607:Intellectual Disability / Q000523:psychology; D007438:Introns / Q000235:genetics; D015810:Linkage Disequilibrium; D008593:Menopause / Q000502:physiology; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D016016:Proportional Hazards Models; D012306:Risk
chemical_list: D001057:Apolipoproteins E; D047629:Estrogen Receptor beta; D004247:DNA