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. 2012:2012:361218.
doi: 10.1155/2012/361218. Epub 2012 Mar 4.

Polymorphisms in HSD17B1: Early Onset and Increased Risk of Alzheimer's Disease in Women with Down Syndrome

Joseph H Lee  1 , Susan Gurney, Deborah Pang, Alexis Temkin, Naeun Park, Sarah C Janicki, Warren B Zigman, Wayne Silverman, Benjamin Tycko, Nicole Schupf
Affiliations

Polymorphisms in HSD17B1: Early Onset and Increased Risk of Alzheimer's Disease in Women with Down Syndrome

Joseph H Lee et al. Curr Gerontol Geriatr Res. 2012.

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.

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Figures

Figure 1
Figure 1
Cumulative incidence of Alzheimer's disease by HSD17B1 rs605059 genotype in women with Down syndrome. TT - - - -. CT……. CC—.
Figure 2
Figure 2
(a) Cumulative incidence of Alzheimer's disease by HSD17B1 rs598126 genotype in women with Down syndrome. TT - - - -. CT……. CC—. (b) Cumulative incidence of Alzheimer's disease by HSD17B1 rs676387 genotype in women with Down syndrome. CC - - - -. CT……. TT—.
Figure 3
Figure 3
Linkage disequilibrium patterns for SNPs in HSD17B1.
See this image and copyright information in PMC

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