{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T17:51:09Z","timestamp":1788544269652,"version":"build-2803163510"},"reference-count":65,"publisher":"Hindawi Limited","license":[{"start":{"date-parts":[[2012,1,1]],"date-time":"2012-01-01T00:00:00Z","timestamp":1325376000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"funder":[{"name":"New York State"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Current Gerontology and Geriatrics Research"],"published-print":{"date-parts":[[2012]]},"abstract":"<jats:p><jats:italic>Background\/Aims<\/jats:italic>. 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 (<jats:italic>HSD17B1<\/jats:italic>) to age at onset and risk of AD.<jats:italic>HSD17B1<\/jats:italic>encodes the enzyme 17\u03b2-hydroxysteroid dehydrogenase (HSD1), which catalyzes the conversion of estrone to estradiol.<jats:italic>Methods<\/jats:italic>. Two hundred and thirty-eight women with DS, nondemented at baseline, 31\u201378 years of age, were followed at 14\u201318-month intervals for 4.5 years. Women were genotyped for 5 haplotype-tagging single-nucleotide polymorphisms (SNPs) in the<jats:italic>HSD17B1<\/jats:italic>gene region, and their association with incident AD was examined.<jats:italic>Results<\/jats:italic>. 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<jats:italic>COASY<\/jats:italic>(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\u20133.1).<jats:italic>Conclusion<\/jats:italic>. These findings support experimental and clinical studies of the neuroprotective role of estrogen.<\/jats:p>","DOI":"10.1155\/2012\/361218","type":"journal-article","created":{"date-parts":[[2012,3,5]],"date-time":"2012-03-05T20:51:54Z","timestamp":1330980714000},"page":"1-8","source":"Crossref","is-referenced-by-count":18,"title":["Polymorphisms in<i>HSD17B1<\/i>: Early Onset and Increased Risk of Alzheimer\u2019s Disease in Women with Down Syndrome"],"prefix":"10.1155","volume":"2012","author":[{"given":"Joseph H.","family":"Lee","sequence":"first","affiliation":[{"name":"The Taub Institute for Research on Alzheimer\u2019s Disease and the Aging Brain, Columbia University Medical Center, New York, NY 10032, USA"},{"name":"Gertrude H. 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