Estrogen Receptor-Beta Variants Are Associated with Increased Risk of Alzheimer’s Disease in Women with Down Syndrome

• Published in: Dementia and geriatric cognitive disorders Vol. 32; no. 4; pp. 241 - 249
• Main Authors: Zhao, Qi, Lee, Joseph H., Pang, Deborah, Temkin, Alexis, Park, Naeun, Janicki, Sarah C., Zigman, Warren B., Silverman, Wayne, Tycko, Benjamin, Schupf, Nicole
• Format: Journal Article
• Language: English
• Published: Basel, Switzerland Karger 01.01.2011; S. Karger AG
• Subjects: Adult; Aged; Alleles; Alzheimer Disease - complications; Alzheimer Disease - genetics; Apolipoproteins E - genetics; Biological and medical sciences; Body Mass Index; Cohort Studies; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Dementia - classification; Dementia - psychology; DNA - genetics; DNA - isolation & purification; Down Syndrome - complications; Down Syndrome - epidemiology; Down Syndrome - genetics; Estrogen Receptor beta - genetics; Ethnic Groups; Female; Genetic Variation; Genotype; Haplotypes; Humans; Intellectual Disability - psychology; Introns - genetics; Linkage Disequilibrium; Medical sciences; Menopause - physiology; Middle Aged; Neurology; Original; Original Research Article; Polymorphism, Single Nucleotide; Proportional Hazards Models; Risk; Vascular diseases and vascular malformations of the nervous system; Estrogen receptor-beta; Down syndrome; Alzheimer’s disease; Estrogen; Chromosomal aberration; Human; Nervous system diseases; Trisomy; Cognitive disorder; Alzheimer disease; Chromosome G21; Aneuploidy; Cerebral disorder; Central nervous system disease; Risk factor; Degenerative disease; Alzheimer's disease
• ISSN: 1420-8008; 1421-9824
• DOI: 10.1159/000334522

Background/Aims: 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. Conclusion: These findings support a role for estrogen and its major brain receptors in modulating susceptibility to AD in women.