Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2014;38(3-4):200-13.
doi: 10.1159/000355559. Epub 2014 Apr 8.

Estrogen receptor α variants affect age at onset of Alzheimer's disease in a multiethnic female cohort

S C Janicki  1 , N Park, R Cheng, L N Clark, J H Lee, N Schupf
Affiliations

Estrogen receptor α variants affect age at onset of Alzheimer's disease in a multiethnic female cohort

S C Janicki et al. Dement Geriatr Cogn Disord. 2014.

Abstract

Background/aims: 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.

PubMed Disclaimer

Figures

Figure 1
Figure 1. Plot of WHICAP participants by AIMs-defined ancestry versus HapMap populations
WHICAP participants Yellow: Predominantly Caucasian AIMs-defined ancestry Green: Admixed/Hispanic AIMs-defined ancestry Blue: Predominantly African AIMs-defined ancestry HapMap populations Light Brown: Ancestrally homogenous Caucasian population (CEPH) Light Blue:Ancestrally homogenous Yoruban Black population (YRI) Red: Ancestrally homogenous East Asian population (CHJA)
Figure 2
Figure 2. Survival curves, ESR1 SNPs associated with incident AD in self-identified Whites
Figure 3
Figure 3. Survival curves, ESR1 SNPs associated with incident AD in self-identified Blacks
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Shughrue PJ, Lane MV, Merchenthaler I. Comparative distribution of estrogen receptor-alpha and -beta mRNA in the rat central nervous system. Journal of Comparative Neurology. 1997;388:507–525. - PubMed
    1. McEwen BS. Invited review: Estrogens effects on the brain: Multiple sites and molecular mechanisms. J Appl Physiol. 2001;91:2785–2801. - PubMed
    1. Goodman Y, Bruce AJ, Cheng B, Mattson MP. Estrogens attenuate and corticosterone exacerbates excitotoxicity, oxidative injury, and amyloid beta-peptide toxicity in hippocampal neurons. J Neurochem. 1996;66:1836–1844. - PubMed
    1. Toran-Allerand CD, Miranda RC, Bentham WD, Sohrabji F, Brown TJ, Hochberg RB, MacLusky NJ. Estrogen receptors colocalize with low-affinity nerve growth factor receptors in cholinergic neurons of the basal forebrain. Proc Natl Acad Sci U S A. 1992;89:4668–4672. - PMC - PubMed
    1. Luine VN. Estradiol increases choline acetyltransferase activity in specific basal forebrain nuclei and projection areas of female rats. Exp Neurol. 1985;89:484–490. - PubMed

Publication types

Substances

Grants and funding