title: Estrogen receptor α variants affect age at onset of Alzheimer's disease in a multiethnic female cohort.
abstract: OBJECTIVE
  Few studies of gene variants that affect estrogen activity investigate their association with age at onset of Alzheimer's disease (AD) in women of different ethnicities. We examined the influence of ESR1 polymorphisms on age at onset of AD in a multiethnic cohort of women.
  
  
  METHODS
  Among 1,436 women participating in the Washington Heights Inwood Columbia Aging Project, association with age at AD onset was assessed for 41 single-nucleotide polymorphisms (SNPs) on the ESR1 gene using Cox proportional hazard models, adjusting for presence of an APOE ε4 allele, years of education, and body mass index.
  
  
  RESULTS
  Six SNPs in self-identified White women were protectively associated with delayed age of AD onset in this self-identified group, including the two restriction fragment length polymorphisms PvuII (rs2234693) and XbaI (rs9340799) (HR range = 0.420-0.483). Two separate SNPs were found to affect age of AD onset in self-identified Black women.
  
  
  CONCLUSIONS
  ESR1 polymorphisms affect age of onset of AD in women, and risk alleles vary by ethnicity. These effects are possibly due to different linkage disequilibrium patterns or differences in comorbid environmental or cultural risk factors mediating the SNP effect on risk for AD.
authors.affiliation: Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Medical Center, New York, N.Y., USA.
authors.forename: S C
authors.initials: SC
authors.lastname: Janicki
authors.forename: N
authors.initials: N
authors.lastname: Park
authors.forename: R
authors.initials: R
authors.lastname: Cheng
authors.forename: L N
authors.initials: LN
authors.lastname: Clark
authors.forename: J H
authors.initials: JH
authors.lastname: Lee
authors.forename: N
authors.initials: N
authors.lastname: Schupf
mesh_terms: D001741:Black or African American / Q000235:genetics; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000544:Alzheimer Disease / Q000453:epidemiology / Q000235:genetics*; D015331:Cohort Studies; D047628:Estrogen Receptor alpha / Q000235:genetics*; D005006:Ethnicity / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006630:Hispanic or Latino / Q000235:genetics; D006801:Humans; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D016016:Proportional Hazards Models; D044465:White People / Q000235:genetics
chemical_list: C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha
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