Comprehensive analysis of APOE and selected proximate markers for late-onset Alzheimer's disease:: Patterns of linkage disequilibrium and disease/marker association
Comprehensive analysis of APOE and selected proximate markers for late-onset Alzheimer's disease:: Patterns of linkage disequilibrium and disease/marker association
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DOI：
10.1016/j.ygeno.2007.02.002
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发表时间：
2007-06-01
期刊：
影响因子：
4.4
通讯作者：
Schellenberg, Gerard D.
中科院分区：
文献类型：
--
作者：
Yu, Chang-En;Seltman, Howard;Schellenberg, Gerard D.
载脂蛋白E的α（4）等位基因使迟发性阿尔茨海默病（LOAD）的风险增加2 - 4倍，但LOAD的病理学并不完全符合载脂蛋白E。可以想象，与载脂蛋白E相近的遗传变异会导致LOAD风险。因此，我们研究了连锁不平衡（LD）的程度，一个全面的50个SNPs的载脂蛋白E和周围使用大量的高加索人样本的1100条染色体。进一步对APOE中的SNPs进行分子单倍型分析以确定其相位。TOMM 40中的一组SNPs，大约在APOE上游15 kb处，显示出与α（4）等位基因的有趣的LD，并且与发生LOAD的风险密切相关。然而，当所有的SNPs都进入logit模型时，只有APOE α的影响仍然显著。这些观察结果减少了TOMM 40基因位点可能对高加索人LOAD风险产生重大影响的可能性。(c)2007年爱思唯尔公司All rights reserved.
The epsilon(4) allele of APOE confers a two- to fourfold increased risk for late-onset Alzheimer's disease (LOAD), but LOAD pathology does not all fit neatly around APOE. It is conceivable that genetic variation proximate to APOE contributes to LOAD risk. Therefore, we investigated the degree of linkage disequilibrium (LD) for a comprehensive set of 50 SNPs in and surrounding APOE using a substantial Caucasian sample of 1100 chromosomes. SNPs in APOE were further molecularly haplotyped to determine their phases. One set of SNPs in TOMM40, roughly 15 kb upstream of APOE, showed intriguing LD with the epsilon(4) allele and was strongly associated with the risk for developing LOAD. However, when all the SNPs were entered into a logit model, only the effect of APOE epsilon(4) remained significant. These observations diminish the possibility that loci in the TOMM40 gene may have a major effect on the risk for LOAD in Caucasians. (c) 2007 Elsevier Inc. All rights reserved.