Apolipoprotein E-491 promoter polymorphism is an independent risk factor for Alzheimer's disease in the Chinese population

Polymorphisms at positions -491, -427 and -219 in the promoter region of the Apolipoprotein E APOE gene have been variously reported to confer an increased risk of developing Alzheimer's disease (AD) independent of the effect of epsilon2, 3 or 4 alleles in exon 4. In order to assess APOE promoter polymorphisms as independent risk factors in AD we have compared results in 183 definite or probable AD cases with 133 controls. We assayed markers at sites -491, -427, -219, and +113 in APOE gene and a polymorphic HIM I site in the nearby APOC1 gene. We found that APOE promoter polymorphisms and APOC1 insertion alleles were significantly associated with AD. However, after stratification for epsilon4 allele, only the A allele at -491 in APOE remained significantly associated with AD. The effects of the other markers depended almost entirely upon linkage disequilibrium with epsilon4 allele, and only trends remained when cases and controls were stratified for the presence or absence of epsilon4 allele. This occurred irrespective of whether markers were examined separately or together as haplotypes. So in the Chinese population only APOE -491 promoter alleles confer significant risk of AD independent of epsilon4 status. (C) 2003 Elsevier Ireland Ltd. All rights reserved.