Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Qingdao, Shandong Province 266071, PR China.
Brain Res. 2011 Mar 24;1381:202-7. doi: 10.1016/j.brainres.2011.01.007. Epub 2011 Jan 12.
The amyloid beta-protein (A-β) deposits in the brains of patients with Alzheimer's disease (AD) are closely associated with innate immune responses that were assumed to play a pivotal role in the pathogenesis of AD. Toll-like receptor 4 (TLR4) is thought to contribute to Aβ clearance. Studies have reported the presence and functional significance of the TLR4/11367 polymorphism in a Han Chinese population. To evaluate the involvement of the TLR4/11367 polymorphism in the risk of late-onset Alzheimer's disease (LOAD), we performed a case-control study to analyze the genotype and allele distributions of the TLR4/11367 polymorphism in a Han Chinese population (137 LOAD cases and 137 healthy controls). There were significant differences in genotype and allele frequencies between LOAD cases and controls (genotype P<0.001, allele P<0.001). After stratification by APOE ε4-carrying status, the C allele of the TLR4/11367 polymorphism was still significantly associated with LOAD in APOE ε4 non-carriers (OR=5.77, 95% CI=3.03-11.00, P<0.001) and carriers (OR=2.03, 95% CI=1.03-3.98, P=0.04). In addition, a logistic regression analysis also conferred positive association between TLR4/11367C and LOAD (dominant model: ORa=3.08, 95% CI=1.60-5.93, P=0.001; recessive model: ORa=8.79, 95% CI=3.31-23.36, P<0.001; additive model: ORa=2.75, 95% CI=1.73-4.37, P<0.001) after adjustment for age, gender, and the APOE ε4 carrier status. This study gives the first evidence that the TLR4/11367 polymorphism was associated with LOAD in a Han Chinese population.
淀粉样β-蛋白（A-β）在阿尔茨海默病（AD）患者大脑中的沉积与固有免疫反应密切相关，固有免疫反应被认为在 AD 的发病机制中起关键作用。Toll 样受体 4（TLR4）被认为有助于 Aβ的清除。研究报告称，TLR4/11367 多态性在汉族人群中存在且具有功能意义。为了评估 TLR4/11367 多态性在晚发性阿尔茨海默病（LOAD）发病风险中的作用，我们进行了一项病例对照研究，以分析汉族人群中 TLR4/11367 多态性的基因型和等位基因分布（137 例 LOAD 病例和 137 例健康对照）。LOAD 病例和对照组在基因型和等位基因频率上存在显著差异（基因型 P<0.001，等位基因 P<0.001）。在 APOE ε4 携带状态分层后，TLR4/11367 多态性的 C 等位基因在 APOE ε4 非携带者（OR=5.77，95%CI=3.03-11.00，P<0.001）和携带者（OR=2.03，95%CI=1.03-3.98，P=0.04）中仍与 LOAD 显著相关。此外，逻辑回归分析也显示 TLR4/11367C 与 LOAD 之间存在正相关（显性模型：ORa=3.08，95%CI=1.60-5.93，P=0.001；隐性模型：ORa=8.79，95%CI=3.31-23.36，P<0.001；加性模型：ORa=2.75，95%CI=1.73-4.37，P<0.001），在调整年龄、性别和 APOE ε4 携带状态后。这项研究首次提供了证据表明 TLR4/11367 多态性与汉族人群中的 LOAD 有关。
