title: Polymorphisms in HSD17B1: Early Onset and Increased Risk of Alzheimer's Disease in Women with Down Syndrome.
abstract: Background/Aims. Genetic variants that affect estrogen activity may influence the risk of Alzheimer's disease (AD). In women with Down syndrome, we examined the relation of polymorphisms in hydroxysteroid-17beta-dehydrogenase (HSD17B1) to age at onset and risk of AD. HSD17B1 encodes the enzyme 17β-hydroxysteroid dehydrogenase (HSD1), which catalyzes the conversion of estrone to estradiol. Methods. Two hundred and thirty-eight women with DS, nondemented at baseline, 31-78 years of age, were followed at 14-18-month intervals for 4.5 years. Women were genotyped for 5 haplotype-tagging single-nucleotide polymorphisms (SNPs) in the HSD17B1 gene region, and their association with incident AD was examined. Results. Age at onset was earlier, and risk of AD was elevated from two- to threefold among women homozygous for the minor allele at 3 SNPs in intron 4 (rs676387), exon 6 (rs605059), and exon 4 in COASY (rs598126). Carriers of the haplotype TCC, based on the risk alleles for these three SNPs, had an almost twofold increased risk of developing AD (hazard ratio = 1.8, 95% CI, 1.1-3.1). Conclusion. These findings support experimental and clinical studies of the neuroprotective role of estrogen.
authors.affiliation: The Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Medical Center, New York, NY 10032, USA.
authors.forename: Joseph H
authors.initials: JH
authors.lastname: Lee
authors.forename: Susan
authors.initials: S
authors.lastname: Gurney
authors.forename: Deborah
authors.initials: D
authors.lastname: Pang
authors.forename: Alexis
authors.initials: A
authors.lastname: Temkin
authors.forename: Naeun
authors.initials: N
authors.lastname: Park
authors.forename: Sarah C
authors.initials: SC
authors.lastname: Janicki
authors.forename: Warren B
authors.initials: WB
authors.lastname: Zigman
authors.forename: Wayne
authors.initials: W
authors.lastname: Silverman
authors.forename: Benjamin
authors.initials: B
authors.lastname: Tycko
authors.forename: Nicole
authors.initials: N
authors.lastname: Schupf