Taub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, NY, USA Gertrude H. Sergievsky Center, College of Physicians & Surgeons, Columbia University, New York, NY, USA Department of Neurology, College of Physicians & Surgeons, Columbia University, New York, NY, USA.
Taub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, NY, USA Gertrude H. Sergievsky Center, College of Physicians & Surgeons, Columbia University, New York, NY, USA.
J Alzheimers Dis. 2014;40(1):83-93. doi: 10.3233/JAD-130551.
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 investigated the influence of ESR2 polymorphisms on age at onset of AD in a multiethnic cohort of women.
To determine whether gene variants would affect risk for AD differently in women of different population ancestries.
Among 1,686 women participating in the Washington Heights Inwood Columbia Aging Project (WHICAP), association with risk for AD was assessed for 20 ESR2 single-nucleotide polymorphisms (SNPs) using multivariate logistic regression, adjusting for age at time of study enrollment, presence of an APOE ε4 allele, years of education, and body mass index.
Increased risk for AD was associated with four ESR2 SNPs in women of predominantly Caucasian AIMS-defined ancestry: rs944045, rs1256062, rs10144225, and rs2274705 (OR range 1.6-1.9, empiric p-value range 0.002-0.004). A separate SNP (rs10137185) was associated with decreased risk for AD in women who identified themselves as Black (OR 0.6, 95% CI = 0.4-0.9). When vascular risk factors were included in the model, a separate SNP (rs1256059) was associated with increased risk for AD in women of admixed/Hispanic ancestry (OR 1.5, 95% CI = 1.1-2.4).
ESR2 polymorphisms affect risk for AD in women, and risk alleles vary by AIMs-defined ancestry and self-identified ethnicity. These effects are possibly due to different linkage disequilibrium patterns or differences in comorbid risk factors mediating SNP effect on risk for AD by group.
很少有研究雌激素活性相关基因变异与不同族裔女性阿尔茨海默病（AD）发病年龄的关系。我们研究了多民族女性 ESR2 多态性对 AD 发病年龄的影响。
确定基因变异是否会对不同人群女性的 AD 风险产生不同的影响。
在参加华盛顿高地-因伍德哥伦比亚老龄化项目（WHICAP）的 1686 名女性中，使用多变量逻辑回归评估 20 个 ESR2 单核苷酸多态性（SNP）与 AD 风险的相关性，调整了研究入组时的年龄、APOE ε4 等位基因、受教育年限和体重指数。
在主要为白种人 AIMS 定义的祖源的女性中，与 AD 风险增加相关的 ESR2 四个 SNP 为：rs944045、rs1256062、rs10144225 和 rs2274705（OR 范围 1.6-1.9，经验 p 值范围 0.002-0.004）。另一个 SNP（rs10137185）与黑人女性 AD 风险降低相关（OR 0.6，95%CI=0.4-0.9）。当将血管危险因素纳入模型时，另一个 SNP（rs1256059）与混合/西班牙裔祖源的女性 AD 风险增加相关（OR 1.5，95%CI=1.1-2.4）。
ESR2 多态性影响女性 AD 风险，风险等位基因因 AIMS 定义的祖源和自我认定的种族而不同。这些影响可能是由于不同的连锁不平衡模式或不同的共病风险因素对 SNP 对 AD 风险的影响在不同人群中不同。
