Laws S M, Taddei K, Martins G, Paton A, Fisher C, Clarnette R, Hallmayer J, Brooks W S, Gandy S E, Martins R N
Department of Surgery, University of Western Australia, Perth, Australia.
Neuroreport. 1999 Mar 17;10(4):879-82. doi: 10.1097/00001756-199903170-00038.
Recent evidence suggests that a polymorphism in the regulatory region of the apolipoprotein E gene (APOE) is associated with an increased risk for developing Alzheimer's disease (AD) independent of that conveyed by the epsilon4 allele of APOE. Previous work by our group indicated that plasma apolipoprotein E (apoE) levels were elevated in AD, raising the possibility that the -491 genotype might modify AD risk by increasing expression of the APOE gene. In a total of 638 individuals the -491AA genotype was significantly associated with AD (P < 0.005) while the TT genotype was associated with controls (P < 0.005). In 138 individuals the AA genotype showed significantly higher plasma apoE levels, independent of epsilon4 and AD status (P < 0.01) as well as within control and AD groups (P < 0.05). Within the AD group the AA genotype showed increased apoE levels when compared to AA controls (P < 0.0001). These results suggest that the -491 AA genotype is associated with increased plasma apoE levels, providing a potential basis for elucidating how that genotype increases the risk for developing AD.
最近的证据表明，载脂蛋白E基因（APOE）调控区域的多态性与患阿尔茨海默病（AD）的风险增加有关，且独立于APOE的ε4等位基因所带来的风险。我们小组之前的研究表明，AD患者血浆载脂蛋白E（apoE）水平升高，这增加了-491基因型可能通过增加APOE基因表达来改变AD风险的可能性。在总共638名个体中，-491AA基因型与AD显著相关（P < 0.005），而TT基因型与对照组相关（P < 0.005）。在138名个体中，AA基因型的血浆apoE水平显著更高，与ε4和AD状态无关（P < 0.01），在对照组和AD组中也是如此（P < 0.05）。在AD组中，与AA对照组相比，AA基因型的apoE水平升高（P < 0.0001）。这些结果表明，-491 AA基因型与血浆apoE水平升高有关，为阐明该基因型如何增加患AD风险提供了潜在依据。
