The -491A/T apolipoprotein E promoter polymorphism association with Alzheimer's disease: independent risk and linkage disequilibrium with the known APOE polymorphism

被引:54
作者
Town, T
Paris, D
Fallin, D
Duara, R
Barker, W
Gold, M
Crawford, F
Mullan, M
机构
[1] Univ S Florida, Dept Psychiat, Roskamp Labs, Tampa, FL 33513 USA
[2] Univ Miami, Sch Med, Mt Sinai Memory Disorder Clin, Miami, FL USA
[3] Univ S Florida, Dept Neurol, Tampa, FL 33620 USA
关键词
Alzheimer's disease; apolipoprotein E; -491A/T polymorphism; genetic association; linkage disequilibrium; independent risk;
D O I
10.1016/S0304-3940(98)00567-9
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
The epsilon 4 allele of the apolipoprotein E gene (APOE) has repeatedly been associated with increased risk for Alzheimer's disease (AD). Bullido and colleagues recently identified a polymorphism in the promoter region of the APOE gene (-491A/T) and found that -491A homozygosity predicted AD independently of APOE epsilon 4. Since the -491A/T polymorphism and the known APOE polymorphism must be in tight linkage disequilibrium, and the later polymorhism is know to be associated with the disease, we wished to determine to what extent this linkage disequilibrium explained the -491A/T polymorphism association with Alzheimer's disease. We genotyped a community-based control sample (n = 132) and a clinic-based Alzheimer's disease sample (n = 190) for the known APOE and -491A/T polymorphisms, and find that, while the -491A/T polymorphism confers some independent risk for AD, linkage disequilibrium between the known APOE and -491A/T polymorphic sites explains most of the -491A association. Furthermore, when considering the known APOE and -491A/T polymorphisms alone, APOE epsilon 4 status is the best predictor of the disease. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved
引用
收藏
页码:95 / 98
页数:4
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