Panza Francesco, D'Introno Alessia, Colacicco Anna M, Capurso Cristiano, Basile Anna M, Capurso Sabrina, Capurso Antonio, Solfrizzi Vincenzo
Department of Geriatrics, Center for Aging Brain, Memory Unit, University of Bari, Policlinico, Piazza Giulio Cesare 11, 70124 Bari, Italy.
Am J Med Genet B Neuropsychiatr Genet. 2004 Apr 1;126B(1):69-73. doi: 10.1002/ajmg.b.20146.
The low density lipoprotein receptor-related protein 1 (LRP1 gene) is a candidate gene for Alzheimer's disease (AD), because it is a ligand for proteins involved in AD pathogenesis, such as apolipoprotein E (APOE), alpha2-macroglobulin (A2M), amyloid precursor protein (APP), and is located on chromosome 12, within a region linked with AD. An association between a silent polymorphism (C/T) in exon 3 and late onset AD has been reported, with an increased frequency of the C allele, although with conflicting results. We examined this polymorphism in a cohort of 166 sporadic AD patients and 225 sex- and age-matched nondemented controls from Southern Italy. No statistically significant differences were found in LRP1 genotype and allele frequencies between the whole AD sample and controls, nor in early- and late-onset subsets of AD patients. No statistically significant differences in frequencies between LRP1 alleles and AD among APOE allele, age, or gender strata were found. Finally, comparing our results with the findings from other European populations, the LRP1 C allele frequency showed a statistically significant decreasing trend from Northern to Southern regions of Europe, with a concomitant increase in LRP1 T allele frequency, but in AD patients only. Finally, in the AD sample, a decreasing geographical trend from North to South of Europe was found for LRP1 CC genotype, and an inverse trend for LRP1 CT genotype frequency. We suggest that these regional variations in LRP1 genotype and allele frequencies in AD could be related to the different patterns of association between this polymorphism and the disease in various European studies.
低密度脂蛋白受体相关蛋白1（LRP1基因）是阿尔茨海默病（AD）的一个候选基因，因为它是参与AD发病机制的蛋白质的配体，如载脂蛋白E（APOE）、α2-巨球蛋白（A2M）、淀粉样前体蛋白（APP），并且位于12号染色体上与AD相关的区域内。尽管结果存在矛盾，但已有报道称外显子3中的一个沉默多态性（C/T）与晚发型AD有关，C等位基因频率增加。我们在一组来自意大利南部的166例散发性AD患者和225例性别和年龄匹配的非痴呆对照中检测了这种多态性。在整个AD样本与对照之间，以及AD患者的早发型和晚发型亚组之间，LRP1基因型和等位基因频率均未发现统计学上的显著差异。在APOE等位基因、年龄或性别分层中，LRP1等位基因与AD之间的频率也未发现统计学上的显著差异。最后，将我们的结果与其他欧洲人群的研究结果进行比较，LRP1 C等位基因频率在欧洲从北部到南部地区呈现出统计学上显著的下降趋势，同时LRP1 T等位基因频率增加，但仅在AD患者中如此。最后，在AD样本中，LRP1 CC基因型从欧洲北部到南部呈现出下降的地理趋势，而LRP1 CT基因型频率则呈现相反的趋势。我们认为，AD中LRP1基因型和等位基因频率的这些区域差异可能与不同欧洲研究中该多态性与疾病之间的不同关联模式有关。
