Lendon C L, Talbot C J, Craddock N J, Han S W, Wragg M, Morris J C, Goate A M
Department of Psychiatry, Washington University Medical School, St Louis, MO 63110, USA.
Neurosci Lett. 1997 Feb 7;222(3):187-90. doi: 10.1016/s0304-3940(97)13381-x.
The epsilon 4 allele of the apolipoprotein E gene (ApoE) is associated with an increased risk for sporadic and some familial forms of Alzheimer's disease (AD) but the precise mechanism of pathogenesis is unknown. ApoE is a ligand for at least three receptors in the central nervous system, low density lipoprotein receptor (LDL-R), very low density lipoprotein receptor VLDL-R and low density lipoprotein-like receptor (LRP). We have tested for association between these receptors and dementia of the Alzheimer's type (DAT) in a clinically based sample of Caucasian cases and age-matched controls. In contrast to findings in a Japanese cohort we detected no association between DAT and a polymorphism in the VLDL-R gene. No association was detected with the LDL-R gene. We observed a possible association between the 87 allele of a polymorphism within the LRP gene and DAT which remained significant after correction for multiple testing. When the effects of known risk factors for AD such as ApoE epsilon 4 were applied, the effect of LRP no longer reached conventional levels of statistical significance. Nevertheless, LRP is a plausible candidate gene and we may be observing a minor risk factor that will require further examination in other large independent samples to assess whether it truly modifies susceptibility to DAT.
载脂蛋白E基因（ApoE）的ε4等位基因与散发性及某些家族性阿尔茨海默病（AD）的发病风险增加相关，但发病的确切机制尚不清楚。ApoE是中枢神经系统中至少三种受体的配体，即低密度脂蛋白受体（LDL-R）、极低密度脂蛋白受体（VLDL-R）和低密度脂蛋白样受体（LRP）。我们在一组以临床为基础的白种人病例及年龄匹配的对照样本中，检测了这些受体与阿尔茨海默型痴呆（DAT）之间的关联性。与日本队列研究结果相反，我们未检测到DAT与VLDL-R基因多态性之间存在关联。也未检测到与LDL-R基因的关联。我们观察到LRP基因内一个多态性的87等位基因与DAT之间可能存在关联，在进行多重检验校正后该关联仍然显著。当应用AD已知风险因素如ApoE ε4的影响时，LRP的影响不再达到传统的统计学显著水平。然而，LRP是一个合理的候选基因，我们可能正在观察到一个较小的风险因素，这需要在其他大型独立样本中进一步研究，以评估它是否真的会改变对DAT的易感性。
