Janicki S C, Park N, Cheng R, Clark L N, Lee J H, Schupf N
Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Medical Center, New York, N.Y., USA.
Dement Geriatr Cogn Disord. 2014;38(3-4):200-13. doi: 10.1159/000355559. Epub 2014 Apr 8.
BACKGROUND/AIMS: Few studies of gene variants that affect estrogen activity investigate their association with age at onset of Alzheimer's disease (AD) in women of different ethnicities. We examined the influence of ESR1 polymorphisms on age at onset of AD in a multiethnic cohort of women.
Among 1,436 women participating in the Washington Heights Inwood Columbia Aging Project, association with age at AD onset was assessed for 41 single-nucleotide polymorphisms (SNPs) on the ESR1 gene using Cox proportional hazard models, adjusting for presence of an APOE ε4 allele, years of education, and body mass index.
Six SNPs in self-identified White women were protectively associated with delayed age of AD onset in this self-identified group, including the two restriction fragment length polymorphisms PvuII (rs2234693) and XbaI (rs9340799) (HR range = 0.420-0.483). Two separate SNPs were found to affect age of AD onset in self-identified Black women.
ESR1 polymorphisms affect age of onset of AD in women, and risk alleles vary by ethnicity. These effects are possibly due to different linkage disequilibrium patterns or differences in comorbid environmental or cultural risk factors mediating the SNP effect on risk for AD.
背景/目的：很少有关于影响雌激素活性的基因变异的研究探讨其与不同种族女性阿尔茨海默病（AD）发病年龄的关联。我们在一个多民族女性队列中研究了ESR1基因多态性对AD发病年龄的影响。
在参与华盛顿高地因伍德哥伦比亚衰老项目的1436名女性中，使用Cox比例风险模型评估ESR1基因上41个单核苷酸多态性（SNP）与AD发病年龄的关联，并对APOE ε4等位基因的存在、受教育年限和体重指数进行了调整。
在自我认定为白人的女性中，六个SNP与该群体中AD发病年龄延迟存在保护性关联，包括两个限制性片段长度多态性PvuII（rs2234693）和XbaI（rs9340799）（风险比范围=0.420-0.483）。在自我认定为黑人的女性中发现了两个独立的SNP影响AD发病年龄。
ESR1基因多态性影响女性AD发病年龄，且风险等位基因因种族而异。这些影响可能是由于不同的连锁不平衡模式或共病环境或文化风险因素的差异介导了SNP对AD风险的影响。
