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

摘要: Background/Aims. Genetic variants that affect estrogen activity may influence the risk of Alzheimer's disease (AD). In women with Down syndrome, we examined relation polymorphisms in hydroxysteroid-17beta-dehydrogenase (HSD17B1) to age at onset and AD. HSD17B1 encodes enzyme 17β-hydroxysteroid dehydrogenase (HSD1), which catalyzes conversion estrone estradiol. Methods. Two hundred thirty-eight DS, nondemented baseline, 31–78 years age, were followed 14–18-month intervals for 4.5 years. Women genotyped 5 haplotype-tagging single-nucleotide (SNPs) gene region, their association incident AD was examined. Results. Age earlier, elevated from two- threefold among homozygous minor allele 3 SNPs intron 4 (rs676387), exon 6 (rs605059), COASY (rs598126). Carriers haplotype TCC, based on alleles these three SNPs, had an almost twofold increased developing (hazard ratio = 1.8, 95% CI, 1.1–3.1). Conclusion. These findings support experimental clinical studies neuroprotective role estrogen.