Estrogen receptor-beta variants are associated with increased risk of Alzheimer's disease in women with Down syndrome

TY - JOUR

T1 - Estrogen receptor-beta variants are associated with increased risk of Alzheimer's disease in women with Down syndrome

AU - Zhao, Qi

AU - Lee, Joseph H.

AU - Pang, Deborah

AU - Temkin, Alexis

AU - Park, Naeun

AU - Janicki, Sarah C.

AU - Zigman, Warren B.

AU - Silverman, Wayne

AU - Tycko, Benjamin

AU - Schupf, Nicole

PY - 2012/2

Y1 - 2012/2

N2 - 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.

AB - 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.

KW - Alzheimer's disease

KW - Down syndrome

KW - Estrogen

KW - Estrogen receptor-beta

UR - https://www.scopus.com/pages/publications/82955165876

U2 - 10.1159/000334522

DO - 10.1159/000334522

M3 - Article

C2 - 22156442

SN - 1420-8008

VL - 32

SP - 241

EP - 249

JO - Dementia and Geriatric Cognitive Disorders

JF - Dementia and Geriatric Cognitive Disorders

IS - 4

ER -