Estrogen receptor-alpha variants increase risk of Alzheimer's disease in women with Down syndrome.

Abstract

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.

• Authors: Nicole Schupf, Joseph H Lee, Michelle Wei, Deborah Pang, Constance Chace, Rong Cheng, Warren B Zigman, Benjamin Tycko, Wayne Silverman
• Journal: Dementia and geriatric cognitive disorders (Dement Geriatr Cogn Disord) Vol. 25 Issue 5 Pg. 476-82 ( 2008) ISSN: 1421-9824 [Electronic] Switzerland
• PMID: 18408366 (Publication Type: Journal Article)
• Copyright: (c) 2008 S. Karger AG, Basel

Chemical References

• Apolipoprotein E4
• Estrogen Receptor alpha

Topics

• Adult
• Aged
• Alzheimer Disease (epidemiology, genetics)
• Apolipoprotein E4 (genetics)
• Down Syndrome (epidemiology, genetics)
• Estrogen Receptor alpha (genetics)
• Female
• Gene Frequency
• Genetic Predisposition to Disease (epidemiology)
• Genotype
• Humans
• Middle Aged
• Polymorphism, Single Nucleotide
• Risk Factors