Cai X, Fallin D, Stanton J, Scibelli P, Duara R, Crawford F, Mullan M
Department of Psychiatry and Behavioral Medicine, University of South Florida College of Medicine, Tampa 33613, USA.
Am J Med Genet. 1997 Jul 25;74(4):365-9.
Although previous association studies have demonstrated that the APOE4 allele is a risk factor for Alzheimer's disease (AD), its value for the prediction of AD in individuals is <100%. The limited predictive value of epsilon4 is also seen in multiply affected families where the epsilon4 allele is not tightly linked to AD. We analyzed a large pedigree multiply affected with AD by lod score linkage analysis at the known loci associated with AD. In this pedigree, the APOE/APOCI gene area was linked to the development of AD, while no linkage was detected to any of the other loci known to be associated with the disease. In this family, then, the inheritance of an epsilon4 allele is highly associated with the early development of the disease (mean age of onset, 62 years), and is a good predictor of disease. However, given the wealth of evidence for association, but not linkage, of APOE4 to AD, we believe this finding suggests that another factor (or factors) interact(s) with APOE to precipitate early disease, and produce positive linkage results. The nature of this factor presently remains unknown.
尽管先前的关联研究表明，APOE4等位基因是阿尔茨海默病（AD）的一个风险因素，但其在个体中预测AD的价值<100%。在多个受影响的家族中也观察到ε4的预测价值有限，在这些家族中，ε4等位基因与AD的联系并不紧密。我们通过对数优势计分连锁分析，在已知与AD相关的位点，对一个多个成员受AD影响的大家系进行了分析。在这个家系中，APOE/APOCI基因区域与AD的发生相关，而在已知与该疾病相关的任何其他位点均未检测到连锁关系。因此，在这个家族中，ε4等位基因的遗传与疾病的早期发生高度相关（平均发病年龄为62岁），是疾病的一个良好预测指标。然而，鉴于有大量证据表明APOE4与AD存在关联而非连锁关系，我们认为这一发现表明，另一个因素（或多个因素）与APOE相互作用，促使疾病早期发生，并产生阳性连锁结果。目前，这个因素的性质尚不清楚。
