Kölsch Heike, Ptok Ursula, Mohamed Iman, Schmitz Sandra, Rao Marie Luise, Maier Wolfgang, Heun Reinhard
Department of Psychiatry, University of Bonn, Bonn, Germany.
Am J Med Genet B Neuropsychiatr Genet. 2003 Aug 15;121B(1):128-30. doi: 10.1002/ajmg.b.20043.
The low-density lipoprotein receptor-related protein (LRP) is one of the most important cholesterol receptors in the brain. Gene variation of its ligand, apolipoprotein E, is a major genetic risk-factor for Alzheimer's disease (AD). The C-allele of the silent C766T polymorphism in exon 3 of the LRP gene might be associated with AD, however, results are conflicting and thus discussed controversially. Consequently, we compared the prevalence of this polymorphism in a homogenous cohort of patients with AD and control subjects. We found that carriers of a C-allele were at lower risk of AD; in agreement with this observation, AD patients who were carriers of a C-allele presented with a later age at onset of the disease than carriers of the TT genotype. These data suggest that LRP polymorphism influences the risk as well as the age at onset of AD. Our results contrast with other studies which described the C-allele to be a risk-factor for AD, but are in line with a recent publication on the effect of LRP polymorphism on longevity and on the risk for coronary artery disease. Further research on LRP polymorphisms is needed to evaluate their effects on the risk of AD, on coronary artery disease and on longevity.
低密度脂蛋白受体相关蛋白（LRP）是大脑中最重要的胆固醇受体之一。其配体载脂蛋白E的基因变异是阿尔茨海默病（AD）的主要遗传风险因素。LRP基因外显子3中沉默的C766T多态性的C等位基因可能与AD相关，然而，结果相互矛盾，因此存在争议。因此，我们比较了AD患者和对照受试者的同质队列中这种多态性的患病率。我们发现，C等位基因携带者患AD的风险较低；与这一观察结果一致，携带C等位基因的AD患者发病年龄比TT基因型携带者晚。这些数据表明，LRP多态性会影响AD的风险以及发病年龄。我们的结果与其他将C等位基因描述为AD风险因素的研究形成对比，但与最近一篇关于LRP多态性对寿命和冠状动脉疾病风险影响的出版物一致。需要对LRP多态性进行进一步研究，以评估它们对AD风险、冠状动脉疾病和寿命的影响。
