Polymorphisms in HSD17B1: Early onset and increased risk of Alzheimer's disease in women with down syndrome

Joseph H. Lee, Susan Gurney, Deborah Pang, Alexis Temkin, Naeun Park, Sarah C. Janicki, Warren B. Zigman, Wayne Silverman, Benjamin Tycko, Nicole Schupf

Research output: Contribution to journalArticle

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-17β-dehydrogenase (HSD17B1) to age at onset and risk of AD. HSD17B1 encodes the enzyme 17-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.

Original languageEnglish (US)
Article number361218
JournalCurrent Gerontology and Geriatrics Research
Volume2012
DOIs
StatePublished - Apr 18 2012

ASJC Scopus subject areas

  • Geriatrics and Gerontology

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    Lee, J. H., Gurney, S., Pang, D., Temkin, A., Park, N., Janicki, S. C., Zigman, W. B., Silverman, W., Tycko, B., & Schupf, N. (2012). Polymorphisms in HSD17B1: Early onset and increased risk of Alzheimer's disease in women with down syndrome. Current Gerontology and Geriatrics Research, 2012, [361218]. https://doi.org/10.1155/2012/361218