Lee Joseph H, Gurney Susan, Pang Deborah, Temkin Alexis, Park Naeun, Janicki Sarah C, Zigman Warren B, Silverman Wayne, Tycko Benjamin, Schupf Nicole
The Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Medical Center, New York, NY 10032, USA.
Curr Gerontol Geriatr Res. 2012;2012:361218. doi: 10.1155/2012/361218. Epub 2012 Mar 4.
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.
背景/目的。影响雌激素活性的基因变异可能会影响阿尔茨海默病（AD）的发病风险。在患有唐氏综合征的女性中，我们研究了羟类固醇-17β-脱氢酶（HSD17B1）基因多态性与AD发病年龄及风险之间的关系。HSD17B1编码17β-羟类固醇脱氢酶（HSD1），该酶催化雌酮转化为雌二醇。方法。对238名年龄在31至78岁之间、基线时无痴呆的唐氏综合征女性进行随访，随访间隔为14至18个月，持续4.5年。对这些女性进行HSD17B1基因区域的5个单倍型标签单核苷酸多态性（SNP）基因分型，并研究它们与AD发病的相关性。结果。第4内含子（rs676387）、第6外显子（rs605059）和COASY第4外显子（rs598126）中3个SNP的次要等位基因纯合女性的发病年龄更早，AD发病风险增加了2至3倍。基于这三个SNP的风险等位基因的单倍型TCC携带者患AD的风险几乎增加了两倍（风险比=1.8，95%可信区间，1.1-3.1）。结论。这些发现支持了雌激素神经保护作用的实验和临床研究。
