title: Lack of independent associations of apolipoprotein E promoter and intron 1 polymorphisms with Alzheimer's disease.
abstract: Several studies have demonstrated genetic associations between Alzheimer's disease (AD) and polymorphisms in the promoter/enhancer regions of the apolipoprotein E (APOE) gene. These studies raise the possibility that APOE transcription control may be involved in altered risks for AD. We evaluated polymorphic sites in the intron-1 enhancer element (IE-1G/C) and in the APOE promoter (-219G/T). For the IE-1 polymorphism, we analyzed 433 individuals (183 AD and 250 controls), and found a strong linkage between the IE-1G allele and APOE-epsilon4. When we controlled for this linkage using log-linear model analysis, we found no independent association between the IE-1 polymorphism and AD. For the -219 polymorphism, we analyzed 475 individuals (168 AD cases, 234 controls, and 73 cases of cerebral amyloid angiopathy (CAA)). We found strong linkages between the -219G allele and APOE-epsilon2 and between the -219 T allele and APOE-epsilon4. Controlling for these linkages, we found no independent association between the -219 polymorphism and AD or CAA. Thus, our studies do not support independent associations between AD and either the IE-1 or the -219 polymorphisms.
authors.affiliation: Alzheimer Research Unit, Massachusetts General Hospital, Charlestown 02129, USA. rebeck@helix.mgh.harvard.edu
authors.forename: G W
authors.initials: GW
authors.lastname: Rebeck
authors.forename: B S
authors.initials: BS
authors.lastname: Cheung
authors.forename: W B
authors.initials: WB
authors.lastname: Growdon
authors.forename: A
authors.initials: A
authors.lastname: Deng
authors.forename: P
authors.initials: P
authors.lastname: Akuthota
authors.forename: J
authors.initials: J
authors.lastname: Locascio
authors.forename: S M
authors.initials: SM
authors.lastname: Greenberg
authors.forename: B T
authors.initials: BT
authors.lastname: Hyman
mesh_terms: D000483:Alleles; D000544:Alzheimer Disease / Q000235:genetics*; D053329:Apolipoprotein E2; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000235:genetics*; D016657:Cerebral Amyloid Angiopathy / Q000235:genetics; D004247:DNA / Q000032:analysis / Q000235:genetics; D017931:DNA Primers; D008040:Genetic Linkage / Q000235:genetics; D006801:Humans; D007438:Introns / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D011401:Promoter Regions, Genetic; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012307:Risk Factors
chemical_list: D053329:Apolipoprotein E2; D053327:Apolipoprotein E4; D001057:Apolipoproteins E; D017931:DNA Primers; D004247:DNA