PMID- 18408366
OWN - NLM
STAT- MEDLINE
DCOM- 20080617
LR  - 20211020
IS  - 1421-9824 (Electronic)
IS  - 1420-8008 (Print)
IS  - 1420-8008 (Linking)
VI  - 25
IP  - 5
DP  - 2008
TI  - Estrogen receptor-alpha variants increase risk of Alzheimer's disease in women 
      with Down syndrome.
PG  - 476-82
LID - 10.1159/000126495 [doi]
AB  - BACKGROUND: Genetic variants that affect estrogen activity may influence the risk 
      of Alzheimer's disease (AD). Two tightly linked polymorphisms (PvuII and XbaI) in 
      the first intron of estrogen receptor 1 (ESR1), the gene for ER-alpha, have been 
      reported to influence estrogen receptor expression and may influence the risk of 
      AD. METHODS: We examined the relation of polymorphisms in ESR1 to the risk of AD 
      in women with Down syndrome. The subjects (181 women with DS, 41-78 years of age) 
      were followed at 14- to 18-month intervals. Information from cognitive 
      assessments, caregiver interviews, medical record reviews and neurological 
      examinations was used to classify dementia. Genomic DNA was genotyped for 5 
      single-nucleotide polymorphisms in the upstream region and the first exon/intron 
      of the ESR1 gene. Their association with dementia risk was evaluated, adjusting 
      for covariates. RESULTS: Women with at least 1 copy of the C allele at rs2234693 
      (PvuII) and those homozygous for the C allele at rs2077647 had an almost 3-fold 
      increase in the risk of AD, compared with women without the C allele. The 
      increased risks were independent of the apolipoprotein E genotype. CONCLUSION: 
      These findings support a role for estrogen receptor activity in the development 
      of AD in women with Down syndrome.
CI  - (c) 2008 S. Karger AG, Basel
FAU - Schupf, Nicole
AU  - Schupf N
AD  - Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia 
      University Medical Center, G.H. Sergievsky Center, New York, NY, USA. 
      ns24@columbia.edu
FAU - Lee, Joseph H
AU  - Lee JH
FAU - Wei, Michelle
AU  - Wei M
FAU - Pang, Deborah
AU  - Pang D
FAU - Chace, Constance
AU  - Chace C
FAU - Cheng, Rong
AU  - Cheng R
FAU - Zigman, Warren B
AU  - Zigman WB
FAU - Tycko, Benjamin
AU  - Tycko B
FAU - Silverman, Wayne
AU  - Silverman W
LA  - eng
GR  - P01 HD035897/HD/NICHD NIH HHS/United States
GR  - U54 HD079123/HD/NICHD NIH HHS/United States
GR  - R01 HD037425-05/HD/NICHD NIH HHS/United States
GR  - P01 HD035897-21/HD/NICHD NIH HHS/United States
GR  - R01 AG014673-08/AG/NIA NIH HHS/United States
GR  - R01 AG014673/AG/NIA NIH HHS/United States
GR  - R01 HD037425/HD/NICHD NIH HHS/United States
PT  - Journal Article
DEP - 20080414
PL  - Switzerland
TA  - Dement Geriatr Cogn Disord
JT  - Dementia and geriatric cognitive disorders
JID - 9705200
RN  - 0 (Apolipoprotein E4)
RN  - 0 (Estrogen Receptor alpha)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Alzheimer Disease/*epidemiology/*genetics
MH  - Apolipoprotein E4/genetics
MH  - Down Syndrome/*epidemiology/*genetics
MH  - Estrogen Receptor alpha/*genetics
MH  - Female
MH  - Gene Frequency
MH  - Genetic Predisposition to Disease/epidemiology
MH  - Genotype
MH  - Humans
MH  - Middle Aged
MH  - Polymorphism, Single Nucleotide
MH  - Risk Factors
PMC - PMC2430887
MID - NIHMS52528
EDAT- 2008/04/15 09:00
MHDA- 2008/06/18 09:00
PMCR- 2008/06/18
CRDT- 2008/04/15 09:00
PHST- 2008/01/23 00:00 [accepted]
PHST- 2008/04/15 09:00 [pubmed]
PHST- 2008/06/18 09:00 [medline]
PHST- 2008/04/15 09:00 [entrez]
PHST- 2008/06/18 00:00 [pmc-release]
AID - 000126495 [pii]
AID - 10.1159/000126495 [doi]
PST - ppublish
SO  - Dement Geriatr Cogn Disord. 2008;25(5):476-82. doi: 10.1159/000126495. Epub 2008 
      Apr 14.