THE -491A T APOLIPOPROTEIN-E PROMOTER POLYMORPHISM ASSOCIATION WITH ALZHEIMERS-DISEASE - INDEPENDENT RISK AND LINKAGE DISEQUILIBRIUM WITH THE KNOWN APOE POLYMORPHISM/

The epsilon 4 allele of the apolipoprotein E gene (APOE) has repeatedl y been associated with increased risk for Alzheimer's disease (AD). Bu llido and colleagues recently identified a polymorphism in the promote r region of the APOE gene (-491A/T) and found that -491A homozygosity predicted AD independently of APOE epsilon 4. Since the -491A/T polymo rphism and the known APOE polymorphism must be in tight linkage disequ ilibrium, and the later polymorhism is know to be associated with the disease, we wished to determine to what extent this linkage disequilib rium explained the -491A/T polymorphism association with Alzheimer's d isease. We genotyped a community-based control sample (n = 132) and a clinic-based Alzheimer's disease sample (n = 190) for the known APOE a nd -491A/T polymorphisms, and find that, while the -491A/T polymorphis m confers some independent risk for AD, linkage disequilibrium between the known APOE and -491A/T polymorphic sites explains most of the -49 1A 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 reserv ed