Alzheimer's Disease And The Apoe Gene And Its Transcriptional Regulatory Region Polymorphism Associated With Analysis

Jiandong Yang (Neurobiology)Directed by Prof. Lin HeAlzheimer disease is the most common cause of dementia. 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 AD independent of the effect of (2, 3 or 4 alleles in exon 4. In order to assess APOE promoter polymorphisms as independent risk factors in Alzheimer's disease (AD) we have compared results in one hundred and eighty three definite or probable AD cases with one hundred and thirty three controls. We assayed markers at sites -491, -427, -219, +113 in APOE gene and a polymorphic Hha1 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 (4 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 (4 allele, and only trends remained when cases and controls were stratified for the presence or absence of (4 allele. This occurred irrespective of whether markers were examined separately or together as haplotypes. So in Chinese population only APOE -491 promoter alleles confer significant risk of AD independent of (4 status.